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Biochemistry International, the initial name of IUBMB Life, was a rapid communication journal published for the International Union of Biochemistry from 1980 to 1992 by Academic Press (Sydney, Australia), an imprint of Harcourt Brace & Company Australia PTY Limited. Biochemistry International was renamed Biochemistry and Molecular Biology International (BAMBI) in 1993 to follow the change of IUB to International Union of Biochemistry and Molecular Biology (IUBMB) when molecular biology content became an essential part of biochemistry. Academic Press published Biochemistry International followed by BAMBI from volume 1 to volume 46, until 1999. With the IUBMB Presidency of William (Bill) Whelan in 1997, it was decided that BAMBI had to undergo significant change so that it could better fulfill its role as a valuable, rapid publication journal concerned with various aspects of Biomolecular Science. Responsibility for the implementation of the change was assigned to Angelo Azzi, in his capacity as the Chair of the IUBMB Committee on Publications. A tender for publication was published and direct information was also sent to many publishers including Blackwell Science Ltd, Portland Press, Springer Verlag, Wiley & Sons Ltd, and Taylor & Francis. All, but Taylor & Francis, answered negatively. Interestingly, one of the negative answers came from Wiley and Sons Ltd., that several years later became the publisher of most of the IUBMB Journals, including IUBMB Life. Keith Courtney, Publishing Director at Taylor & Francis, answered very enthusiastically and a publishing agreement for BAMBI was signed on June 1st, 1998. It was agreed that Taylor & Francis were to be publish volumes 47–49, 1999, in paper form. In August 1999, IUBMB Life replaced BAMBI, Taylor & Francis, became part of Informa PLC, and continued publication until volume 60. With Taylor & Francis, the electronic submission system begun at the end of 2004. Following the difficulties with Informa, such as substantial delays in IUBMB Life publication, text editing errors and mistakes in proofs, the decision was made that a change in publisher was necessary and John Wiley & Sons, Inc. became a potential opportunity, being already the Publisher of another IUBMB Journal Biochemistry and Molecular Biology Education (BAMBED); so, their attractive publishing proposal for IUBMB Life was accepted. The December 2007 issue of IUBMB Life was the last published by Taylor & Francis-Informa, with which a cordial and profitable collaboration was acknowledged. As from January 2008, commencing with volume 60, no. 1, the new publisher was John Wiley & Sons, Inc. Electronic submission continued, using Manuscript Central platform. Print issues ceased with volume 66 in 2014 with only the online version being published. The Publishers have never been just companies but instead persons, with friendly interactions. Starting with Taylor & Frances, the Editors-in-Chief were invited to annual dinner meeting in London, at special restaurants hosted by Keith Courtney, and Beverly Ackerman. Reviews of the past years were presented, and forthcoming plans were discussed, that were later implemented with the aid of Matthew Pacey. The tradition continued in Hoboken, New Jersey, with Wiley & Sons, Ltd and our partners Colette Bean (Associate Publisher), Michael Weston (Associate Editor), and Michael Gates (Figure 1). Jennie Kim, as a successor of Colette Bean, continued this successful practice. With Julia Kossova (successor of Jennie Kim), important initial exchanges (always at a restaurant) were realized in Boston and Cambridge. Anthony (Tony) Linnane (Figure 2) was a highly accomplished scientist in the Department of Biochemistry at Monash University in Melbourne, Australia. As a towering figure of Australian and international Biochemistry, he accomplished exceptional research on the biogenesis of mitochondria and had major roles in the Australian Biochemical Society (ABS, later becoming ASBMB) and the International Union of Biochemistry (IUB, later becoming IUBMB) and in the Federation of Asian and Oceanian Biochemists (FAOB later becoming FAOBMB). Tony Linnane continued the action of his friend Kunio Yagi (former IUB Treasurer and President) who contributed much to improving the finances of the Union. As a part of this process of financial strengthening (he was also Treasurer of IUBMB for 9 years between 1988 and 1999), Tony Linnane founded the journal, Biochemistry International, a rapid publication journal modeled on the highly successful Biochemical and Biophysical Research Communications. Published in Sydney, Tony Linnane was running Biochemistry International from his office at Monash University. Kelvin J. A. Davies (Figure 3) was chosen due to his brilliant experience as founding co-Editor-in-Chief (together with William Austin Pryor until 2003) of the journal Free Radical Biology & Medicine Bill Whelan, Brian Beechey (IUBMB Treasurer), and Angelo Azzi had a meeting with Keith Courtney (Taylor and Francis) in London where it was decided on the transition between the editorship of Anthony Linnane: an agreement was signed to publish volumes 47–49, in 1999 and Kelvin Davies was to be appointed BAMBI Editor-in-Chief as of January 1, 1999. From October 31, 1998 to June 30, 1999, Kelvin Davies received manuscripts to be handled according to the recommendation of the associate editors. From January 1, 1999, Anthony Linnane stayed as member of the editorial board until the board changed to that of IUBMB Life. The name of BAMBI changed with volume 48 on July 1st, 1999 but the volume numbering continued. Till December 31st, 1999, IUBMB Life kept the subtitle “Formerly Biochemistry and Molecular Biology International.” The name change was the result of a conversation by Bill Whelan (IUBMB President) and Angelo Azzi (Chair of the Committee on Publications) had with Kelvin Davis in Santa Barbara in 1998 at a Meeting of the Oxygen Club of California who suggested the new name. The idea was that the name IUBMB Life would be rapidly shortened to “Life” but this in fact did not happen. William J. (Bill) Whelan (Figure 4) became the new co-Editor-in-Chief of IUBMB Life in May 2000 and continued till the end of 2020. The choice of William J. (Bill) Whelan was after the resignation of Kelvin Davies. Although an emergency option, it was in fact the best possible choice of an experienced member of the IUBMB family as the Secretary General FEBS (1965–1967), the Secretary General of PAABS (1970–1972), the IUB General Secretary (1973–1982), and the IUBMB President (1997–2000). Bill Whelan had also an extraordinary experience in publishing, as member of the Biochemical Journal editorial board (1952–1960), Executive Editor of Archives of Biochemistry and Biophysics (1964–1974), Founding Editor of FEBS Letters (1968–1980), Editor-in-Chief of Trends in Biochemical Sciences (1975–1978), and Editor-in-Chief of the FASEB Journal (1986–1996). In accepting the responsibility as editor-in-chief, Bill Whelan put, as a condition that the Chair of the IUBMB Committee on Publications, Angelo Azzi be co-Editor-in-Chief. Angelo Azzi (Figure 5) was elected as Chair of the IUBMB Committee on Publications on recommendation by Brian Clark at the 17th International Congress of Biochemistry and Molecular Biology in conjunction with 1997 annual meeting of the American Society for Biochemistry and Molecular Biology held in San Francisco, California, August 24–29, 1997. In this capacity, he structured the change of BAMBI's publisher from Academic Press to Taylor & Francis, with the nomination of Kelvin Davies as the new Editor-in-Chief and the transfer of BAMBI from Pergamon Press to ASBMB. He also renegotiated a very satisfying agreement with Elsevier for the publication of Trends in Biochemical Sciences (TiBS) and achieved to have Molecular Aspects of Medicine sponsored by IUBMB in exchange for royalties. He also managed to have BioFactors moved from IOS Press to Wiley and Sons, Ltd. He also concluded negotiations with Sigma-Aldrich over the rights to IUBMB-Nicholson Metabolic Maps, Minimaps & Animaps and to provide grants, with the royalties from Sigma-Aldrich, to young scientists wanting to attend IUBMB Conferences. After 9 years as Chair of the IUBMB Committee on Publications, he was elected in 2006 President Elect of the IUBMB; he became President of the IUBMB after 6 months, following the resignation of IUBMB President George Kenyon, and in 2012 he became past-president under the presidency of Gregory Petsko. One of the first moves was a meeting with Corey Gray, Vice President for Editorial and Production at Taylor & Francis, Philadelphia and his colleague Suzanne Colville. There, the detail of the mix of contents to be realized in the future was discussed. The “Reviews,” concise, cutting-edge articles remained the backbone of the journal. The publisher decided not to impose to invited review authors any charge for a reasonable number of color illustrations. Since copy flow was at the minimum, any type of articles needed to be published, and new types were created such as “Worth a Second Look.” The latter were reviews by journals that had relatively small, regional, circulations but which often attracted excellent evaluations. A case in point was the Australian Biochemist, the house organ of the Australian Society for Biochemistry and Molecular Biology. Nick Hoogenraad, the Society officer who had built up the journal, agreed to have IUBMB Life reprinting selected reviews that the authors would be given the opportunity to update. The dream was to have enough spontaneous submissions in order not to worry about closing an issue. In the meantime, fillers were created like “How I Became a Biochemist” (HIBAB), invited short autobiographies, that, besides creating copy flow, became appreciated historical pieces. Similarly, “My Favorite Enzyme,” “What's in The Name,” “Recollections,” and “Errors/Horrors in Biochemistry” were also published. Before the introduction of the electronic submission system at the end of 2004, articles were received in paper form in four copies, two of which were sent out to reviewers. The reviewers were remunerated with a check of $20 per refereed paper, paid out of the editors' honorarium. The members of the Editorial Board were selected during a meeting of the co-Editors-in-Chief taking place in the occasion of the yearly Miami Winter Symposium. The members of the Editorial Board were chosen among established colleagues (some were Nobel Prize awardees) and were performing as excellent reviewers. Some of them have contributed review articles and coordinated special issues. In addition to the Editorial Board members, a board of reviewers was created, following the number of requests from mostly young scientist that considered a reviewer responsibility with IUBMB Life a plus in their biosketches. Most of the technical work was possible due to the help of Sandra Black and Yesim Negis the Assistants to the editors Whelan and Azzi, respectively. It has been a great relationship, where collaboration and friendship were intermingled. One of the ways IUBMB Life has been made visible was by creating special Congress Issues, to be distributed to the IUBMB Congress participants either in their congress bags or at the IUBMB booth. These issues started from the Congress in Birmingham in July 2000 and continued with all the following congress. One remarkable issue was that for the Kyoto Congress dedicated to Osamu Hayaishi, a world-renowned biochemist and the discoverer of oxygenases (Figure 6). Another very special issue was dedicated to the 50th anniversary of the foundation of IUB/IUBMB that was celebrated in 2005 in Budapest at the IUBMB/FEBS meeting (Figure 7). During the time between 2000 and 2020, there has been a massive increase in submissions going from less than 200 to more than 1,600. This was due to several factors, including the better knowledge of the Journal, realized with an effective marketing, especially by Wiley and Sons. Another reason for attraction has been the lack of submission fees and free online color that were becoming progressively less common with the advent of open access journals. A rapid editorial decision, well documented by independent referees had been obviously appreciated and, of course, the increasing impact factor of the Journal had been certainly paralleling the increasing submissions to IUBMB Life. With the copy flow increase, well above the page budget of IUBMB Life, a more effective selection of the best articles could take place: out of 1,607 submissions recorded in 2020, there have been 165 acceptance, with a rejection rate of more than 90%. In fact, the latter figure was the acceptance rate of BAMBI. BAMBI was attributed in 1997 Impact Factor (as devised by Eugene Garfield, the founder of the Institute for Scientific Information [ISI] in 1975) of 0.578. In the year 2000, IUBMB Life Impact Factor is recorded as 0.418. IUBMB Life increased its Impact Factor steadily until 2010, when it peaked at 4.251 and remained stable around 3 in subsequent years. Since Thomson Scientific & Healthcare acquired ISI in 1992 and Clarivate secured Thomson Scientific & Healthcare in 2017, it was Clarivate to attribute to IUBMB Life the last impact factor of 3.244 in 2019. The actors of this piece of history, which have compiled this account, have had a breathtaking and fulfilling 20-year long time. The beginning of IUBMB Life coincided in fact with the booming of publishing initiatives and projecting a little Journal to a competitive international level had been an additional challenge. For both Bill Whelan and Angelo Azzi, IUBMB Life has not been another journal: it was linked, and not only by the name to the most important biological Union, being its flagship publication and, for it, an important source of income. Since the IUBMB is not a society with thousands of members that could contribute to, read and subscribe to the journal, the readership had to be created step by step, in a tough competition with similar short communication journals like FEBS Letters (supported by all European Societies of Biochemistry) and Biochemical and Biophysical Research Communications (the oldest journal of this type, BioQuick in short, that published rapid papers by a photographic procedure). Another challenge has been that of attracting authors to publish in a journal with low Impact Factor, a battle that was won with the help of many friend scientists that “sacrificed” one of their articles to allow IUBMB Life to become a better journal. It has been a time of technical evolution, when delivery and further handling of paper articles by post was replaced by internet, electronic submission, email, and new dimensions were introduced in publishing such as speed and color. It has been a 20-year time when IUBMB, IUBMB Life, the Publishers, the members of the Editorial Board and many authors where not only organizations and names but they have been part of a great, generous and friendly family.

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Abstract The extension of life span by caloric restriction has been studied across species from yeast and C aenorhabditis elegans to primates. No generally accepted theory has been proposed to explain these observations. Here, we propose that the life span extension produced by caloric restriction can be duplicated by the metabolic changes induced by ketosis. From nematodes to mice, extension of life span results from decreased signaling through the insulin/insulin‐like growth factor receptor signaling (IIS) pathway. Decreased IIS diminishes phosphatidylinositol (3,4,5) triphosphate (PIP 3 ) production, leading to reduced PI3K and AKT kinase activity and decreased forkhead box O transcription factor (FOXO) phosphorylation, allowing FOXO proteins to remain in the nucleus. In the nucleus, FOXO proteins increase the transcription of genes encoding antioxidant enzymes, including superoxide dismutase 2, catalase, glutathione peroxidase, and hundreds of other genes. An effective method for combating free radical damage occurs through the metabolism of ketone bodies, ketosis being the characteristic physiological change brought about by caloric restriction from fruit flies to primates. A dietary ketone ester also decreases circulating glucose and insulin leading to decreased IIS. The ketone body, d ‐β‐hydroxybutyrate ( d ‐βHB), is a natural inhibitor of class I and IIa histone deacetylases that repress transcription of the FOXO3a gene. Therefore, ketosis results in transcription of the enzymes of the antioxidant pathways. In addition, the metabolism of ketone bodies results in a more negative redox potential of the NADP antioxidant system, which is a terminal destructor of oxygen free radicals. Addition of d ‐βHB to cultures of C. elegans extends life span. We hypothesize that increasing the levels of ketone bodies will also extend the life span of humans and that calorie restriction extends life span at least in part through increasing the levels of ketone bodies. An exogenous ketone ester provides a new tool for mimicking the effects of caloric restriction that can be used in future research. The ability to power mitochondria in aged individuals that have limited ability to oxidize glucose metabolites due to pyruvate dehydrogenase inhibition suggests new lines of research for preventative measures and treatments for aging and aging‐related disorders. © 2017 The Authors IUBMB Life published by Wiley Periodicals, Inc. on behalf of International Union of Biochemistry and Molecular Biology, 69(5):305–314, 2017

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Vitamin E has been first recognized as an essential molecule by Evans and Bishop almost 100 years ago, and it therefore is appropriate and timely to dedicate a full thematic issue of IUBMB-Life to its still debated and not yet completely elucidated essential and regulatory functions. In search for a specific transporter and receptor of vitamin E many regulatory effects have been identified and it appears that rather than by acting via one specific target, it affects many. Hence, there is good evidence that vitamin E has regulatory roles in the body—but its molecular mechanisms of action are still subject of investigations. Regulatory effects of vitamin E can be antioxidant/prooxidant by means of its redox-active chemical moieties, or non-antioxidant via interaction of its structural body with receptors, transporters, enzymes and transcription factors, and by modulating membranes and membrane domains such as lipid rafts. To exert regulatory effects vitamin E needs to be efficiently taken up from the diet and distributed in the body and the route taken was for long assumed to be mostly governed by its properties as a hydrophobic molecule. Seminal works done over the last decades revealed that only α-tocopherol (one of the eight natural vitamin E analogues [α-, β-, γ-, δ-tocopherols/tocotrienols] is preferentially enriched in the body by the hepatic α-tocopherol transfer protein [αTTP]), whereas the other seven analogues and excess α-tocopherol are not retained and rapidly metabolized. In addition to αTTP, several more proteins have been discovered that interact with vitamin E and distribute it in the body and in cells. Impaired uptake and transport of α-tocopherol due to genetic mutations in specific genes involved in its transport has been recognized as the reason for primary and secondary vitamin E deficiency syndromes, and in particular of ataxia with vitamin E deficiency (AVED), the main vitamin E deficiency syndrome resulting from αTTP mutations signifying the essential function of α-tocopherol for humans. Interestingly, the vitamin E analogues with lower bioavailability and higher metabolism in vivo have often higher activity at lower concentration in vitro despite their equal value as chemical antioxidants, suggesting that their elimination from the body possibly serves to minimize interference with some cellular functions. To unravel at a molecular level the regulatory roles and biological effects of the eight vitamin E analogues and their metabolites, their interactions with enzymes, receptors, membranes and transport proteins and the function of other natural analogues such as alpha-tocopheryl phosphate and alpha-tocopheryl nicotinate as well of a myriad of synthetic derivatives remains a challenging topic for future investigations. As discussed in this issue (issue 71:4 1-11), many cellular regulatory effects of vitamin E and its metabolites have been recognized modulating apoptosis/cell survival, ferroptosis, cell proliferation, angiogenesis, lipid metabolism, membrane properties and repair, long term potentiation, signal transduction and gene expression. These cellular effects often go beyond a simple antioxidant action and most likely contribute to the beneficial regulatory effects of vitamin E observed in a number of diseases and conditions, ranging from atherosclerosis, inflammation, diabetes, obesity, infection, immune regulation, wound healing, ischemia/reperfusion injury, reproduction, age-related macular degeneration (AMD), neurodegeneration, non-alcoholic steatohepatitis (NASH), cancer/metastasis, senescence and aging.

Ornithine decarboxylase (ODC) initiates the polyamine biosynthetic pathway. The amount of ODC is altered in response to many growth factors, oncogenes, and tumor promoters and to changes in polyamine levels. Susceptibility to tumor development is increased in transgenic mice expressing high levels of ODC and is decreased in mice with reduced ODC due to loss of one ODC allele or elevated expression of antizyme, a protein that stimulates ODC degradation. This review describes key factors that contribute to the regulation of ODC levels, which can occur at the levels of transcription, translation, and protein turnover. Ornithine decarboxylase (ODC) initiates the polyamine biosynthetic pathway. The amount of ODC is altered in response to many growth factors, oncogenes, and tumor promoters and to changes in polyamine levels. Susceptibility to tumor development is increased in transgenic mice expressing high levels of ODC and is decreased in mice with reduced ODC due to loss of one ODC allele or elevated expression of antizyme, a protein that stimulates ODC degradation. This review describes key factors that contribute to the regulation of ODC levels, which can occur at the levels of transcription, translation, and protein turnover. l-Ornithine decarboxylase (ODC) 2The abbreviations used are: ODC, l-ornithine decarboxylase; PLP, pyridoxal phosphate; DFMO, α-difluoromethylornithine; NQO1, NAD(P)H quinone oxidoreductase; SSAT, spermidine/spermine N1-acetyltransferase; ORF, open reading frame; UTR, untranslated region; IRES internal ribosome entry site; MEK, mitogen-activated protein kinase/extracellular signal-regulated kinase kinase; ERK, extracellular signal-regulated kinase. catalyzes the first step in the polyamine biosynthetic pathway forming putrescine, which is then converted into the polyamines spermidine and spermine (1Tabor C.W. Tabor H. Annu. Rev. Biochem. 1976; 45: 285-306Crossref PubMed Scopus (996) Google Scholar, 2Pegg A.E. Cancer Res. 1988; 48: 759-774PubMed Google Scholar, 3Gerner E.W. Meyskens Jr., F.L. Nat. Rev. Cancer. 2004; 4: 781-792Crossref PubMed Scopus (897) Google Scholar, 4Cohen S.S. A Guide to the Polyamines. Oxford University Press, New York1998: 231-259Google Scholar) (Fig. 1). In some microorganisms and in plants, putrescine can also be made from arginine via an arginine decarboxylase and subsequent conversion of the agmatine to putrescine. However, evidence for a mammalian arginine decarboxylase is controversial (5Coleman C.S. Hu G. Pegg A.E. Biochem. J. 2004; 379: 849-855Crossref PubMed Google Scholar), and ODC provides the only established route for polyamine synthesis de novo. Polyamine content plays important roles in both normal and neoplastic growth and alterations of polyamine synthesis via changes in ODC content occur in response to tumor promoters and carcinogens (2Pegg A.E. Cancer Res. 1988; 48: 759-774PubMed Google Scholar, 3Gerner E.W. Meyskens Jr., F.L. Nat. Rev. Cancer. 2004; 4: 781-792Crossref PubMed Scopus (897) Google Scholar). ODC is very highly regulated, and ODC activity varies in response to many stimuli. These alterations in activity are brought about by changes in the amount of ODC protein, which turns over very rapidly. ODC degradation is controlled by a protein termed antizyme, which responds to polyamine concentration. ODC is also regulated at the level of transcription and the ODC gene is one of the targets of the Myc/Max transcription factor. A third level of regulation occurs in the translation of ODC mRNA. This brief review discusses these aspects of ODC and some relevant structural and comparative data focusing on relatively recent studies. Summaries of the vast literature describing earlier work on ODC, the myriad of factors altering its activity, and its value as a drug target are contained in previous reviews (2Pegg A.E. Cancer Res. 1988; 48: 759-774PubMed Google Scholar, 3Gerner E.W. Meyskens Jr., F.L. Nat. Rev. Cancer. 2004; 4: 781-792Crossref PubMed Scopus (897) Google Scholar, 4Cohen S.S. A Guide to the Polyamines. Oxford University Press, New York1998: 231-259Google Scholar, 6McCann P.P. Pegg A.E. Pharmacol. Ther. 1992; 54: 195-215Crossref PubMed Scopus (230) Google Scholar). ODC is a pyridoxal phosphate (PLP)-dependent amino acid decarboxylase. Biochemical studies showed that it is a homodimer with two active sites each made up of residues from both subunits (7Coleman C.S. Stanley B.A. Viswanath R. Pegg A.E. J. Biol. Chem. 1994; 269: 3155-3158Abstract Full Text PDF PubMed Google Scholar). Crystallographic determination of the structures of mammalian and Trypanosoma brucei ODCs (8Almrud J.J. Oliveira M.A. Kern A.D. Grishin N.V. Phillips M.A. Hackert M.L. J. Mol. Biol. 2000; 295: 7-16Crossref PubMed Scopus (128) Google Scholar, 9Jackson L.K. Baldwin J. Akella R. Goldsmith E.J. Phillips M.A. Biochemistry. 2004; 43: 12990-12999Crossref PubMed Scopus (33) Google Scholar) confirmed these observations. The structure of eukaryote ODC is that of a group IV decarboxylase, structurally homologous to the bacterial and plant arginine decarboxylases, bacterial diaminopimelic acid decarboxylase, and alanine racemase but unrelated to the bacterial ODCs. Eukaryotic ODCs are, in general, highly specific for l-ornithine with a very weak activity on l-lysine and an even lower activity on l-arginine (10Osterman A. Kinch L.N. Grishin N.V. Phillips M.A. J. Biol. Chem. 1995; 270: 11797-11802Abstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar). However, a homolog was isolated from Paramecium bursaria chlorella virus. This protein has a key amino acid substitution (Glu for Asp) in a residue that forms an interaction with the δ-amino group of ornithine analogs in the x-ray structures of ODC and despite slight ODC activity is actually an arginine decarboxylase (11Shah R. Coleman C.S. Mir K. Baldwin J. J.L. Van Etten Grishin N.V. Pegg A.E. Stanley B.A. Phillips M.A. J. Biol. Chem. 2004; 279: 35760-35767Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar). There are two domains in the ODC monomer, an NH2-terminal domain forming a β/α-barrel that binds the cofactor, and a COOH-terminal domain, which is predominantly a β-sheet structure. The active sites are formed at the dimer interface between the NH2-terminal domain of one subunit and the COOH-terminal domain of the other (8Almrud J.J. Oliveira M.A. Kern A.D. Grishin N.V. Phillips M.A. Hackert M.L. J. Mol. Biol. 2000; 295: 7-16Crossref PubMed Scopus (128) Google Scholar, 9Jackson L.K. Baldwin J. Akella R. Goldsmith E.J. Phillips M.A. Biochemistry. 2004; 43: 12990-12999Crossref PubMed Scopus (33) Google Scholar). One unusual property of ODC is that the association between two subunits is quite weak and the dimers are in rapid equilibrium with inactive monomers even under physiological conditions. The PLP cofactor is bound in a Schiff base linkage to Lys69 (7Coleman C.S. Stanley B.A. Viswanath R. Pegg A.E. J. Biol. Chem. 1994; 269: 3155-3158Abstract Full Text PDF PubMed Google Scholar, 8Almrud J.J. Oliveira M.A. Kern A.D. Grishin N.V. Phillips M.A. Hackert M.L. J. Mol. Biol. 2000; 295: 7-16Crossref PubMed Scopus (128) Google Scholar, 12Jackson L.K. Brooks H.B. Myers D.P. Phillips M.A. Biochemistry. 2003; 42: 2933-2940Crossref PubMed Scopus (30) Google Scholar). It is likely that Cys360 plays an essential role in ensuring correct protonation of the decarboxylated reaction intermediate at Cα. If Cys360 is mutated to Ser or Ala, there is a large reduction in activity (7Coleman C.S. Stanley B.A. Viswanath R. Pegg A.E. J. Biol. Chem. 1994; 269: 3155-3158Abstract Full Text PDF PubMed Google Scholar), and the mutated enzyme becomes a decarboxylation-dependent transaminase due to frequent protonation of C-4′ of the intermediate (12Jackson L.K. Brooks H.B. Myers D.P. Phillips M.A. Biochemistry. 2003; 42: 2933-2940Crossref PubMed Scopus (30) Google Scholar). ODC is readily inactivated by nitric oxide due to the sensitivity of this Cys residue to nitrosylation (13Bauer P.M. Buga G.M. Fukuto J.M. Pegg A.E. Ignarro L.J. J. Biol. Chem. 2001; 276: 34458-34464Abstract Full Text Full Text PDF PubMed Scopus (110) Google Scholar). The most widely used pharmacological inhibitor of ODC is α-difluoromethylornithine (DFMO), a valuable antitrypanosomal agent that acts as an enzyme-activated irreversible inhibitor of ODC forming a covalent adduct with Cys360 (6McCann P.P. Pegg A.E. Pharmacol. Ther. 1992; 54: 195-215Crossref PubMed Scopus (230) Google Scholar). The rapid turnover of ODC is brought about by the 26 S proteasome, but ODC is highly unusual in that ubiquitination is not required for this degradation (Fig. 1). Instead, a non-covalent association with a protein termed antizyme directs ODC to the proteasome (14Hayashi S. Murakami Y. Biochem. J. 1995; 306: 1-10Crossref PubMed Scopus (183) Google Scholar, 15Coffino P. Nat. Rev. Mol. Cell Biol. 2001; 2: 188-194Crossref PubMed Scopus (303) Google Scholar, 16Mangold U. IUBMB Life. 2005; 57: 671-676Crossref PubMed Scopus (77) Google Scholar, 17Kahana C. Asher G. Shaul Y. Cell Cycle. 2005; 4: 1461-1464Crossref PubMed Scopus (47) Google Scholar). Antizyme increases the degradation of ODC by enhancing its interaction with the proteasome but does not increase the rate of proteasomal processing (18Zhang M. Pickart C.M. Coffino P. EMBO J. 2003; 22: PubMed Scopus Google Scholar). of antizyme is not by ODC S. C. J. Biochem. 269: PubMed Scopus Google Scholar) and the antizyme from the at the proteasome is to about degradation of by Coffino and M. M.A. Coffino P. J. Biol. Chem. 2004; 279: Full Text Full Text PDF PubMed Scopus Google Scholar) that actually degradation of ODC at the degradation of mammalian ODC a at the of the This is in brucei ODC, which is A. S. Biochem. 2003; PubMed Google Scholar). of the residues forming the COOH-terminal of mammalian ODC this protein even in the of of these residues to other can (18Zhang M. Pickart C.M. Coffino P. EMBO J. 2003; 22: PubMed Scopus Google Scholar). which is in this COOH-terminal to be a key residue (14Hayashi S. Murakami Y. Biochem. J. 1995; 306: 1-10Crossref PubMed Scopus (183) Google Scholar). of Ser ODC even in the of antizyme (18Zhang M. Pickart C.M. Coffino P. EMBO J. 2003; 22: PubMed Scopus Google Scholar). of the residues also ODC but to a the residues or of (18Zhang M. Pickart C.M. Coffino P. EMBO J. 2003; 22: PubMed Scopus Google Scholar). The structure of the COOH-terminal for rapid degradation of ODC is not this is from the brucei and ODC structures that and is in the structure of the ODC (8Almrud J.J. Oliveira M.A. Kern A.D. Grishin N.V. Phillips M.A. Hackert M.L. J. Mol. Biol. 2000; 295: 7-16Crossref PubMed Scopus (128) Google Scholar, 9Jackson L.K. Baldwin J. Akella R. Goldsmith E.J. Phillips M.A. Biochemistry. 2004; 43: 12990-12999Crossref PubMed Scopus (33) Google Scholar). it is not alterations as Ser on the structure and to this or in this actually be in the degradation a pathway has for ODC degradation which is regulated by NAD(P)H quinone and does not the COOH-terminal domain C. Asher G. Shaul Y. Cell Cycle. 2005; 4: 1461-1464Crossref PubMed Scopus (47) Google Scholar, G. P. Shaul Y. C. Mol. 2005; Full Text Full Text PDF PubMed Scopus Google Scholar). binds to ODC and If this interaction is with it ODC monomers to degradation by the S proteasome in a of both antizyme and The to which this which the S proteasome that only to ODC turnover in other physiological to be but it be in the turnover of ODC Antizyme was first as a inhibitor of ODC that was in response to an increase in polyamine content U. S. A. 1976; PubMed Scopus Google Scholar). This is due to the of the antizyme to the ODC forming a which activity (Fig. 1). The relatively weak association between the ODC subunits in the interaction with studies in the of S. Y. S. Biochem. J. PubMed Google Scholar) showed that of antizyme to a loss of ODC protein and that this is due to an increase in ODC degradation (14Hayashi S. Murakami Y. Biochem. J. 1995; 306: 1-10Crossref PubMed Scopus (183) Google Scholar, 15Coffino P. Nat. Rev. Mol. Cell Biol. 2001; 2: 188-194Crossref PubMed Scopus (303) Google Scholar, 16Mangold U. 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