Philip Coffino, MD, PhD
Professor Emeritus
Microbiology and Immunology
School of Medicine

Education & Training

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• Residency School of Medicine University of California, San Francisco

Websites

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• Profile at UCSF Biomedical Sciences (bms.ucsf.edu)

Grants and Projects

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• Structure of functionally important dynamic states of the proteasome, NIH, 2014-2019
• Bio-Organic Biomedical Mass Spectrometry Resource, NIH, 1982-2015
• Proteasome substrate processing, NIH, 1991-2015
• A novel biochemical nanomotor, NIH, 2009-2012
• Energy production and utilization in the proteasome, NIH, 2005-2010
• Induced Selective Degradation of Cellular Proteins, NIH, 2000-2001
• Gordon Conference on Polyamines, NIH, 1999-2000
• Mechanisms of Ornithine Decarboxylase Regulation, NIH, 1982-1996
• Functional Anatomy of Ornithine Decarboxylase, NIH, 1988-1992
• Faseb Summer Research Conference--Somatic Cell Genetics, NIH, 1986
• Regulation of Yeast Ornithine Decarboxylase Degradation, NIH, 1998-1900

Publications (79)

Top publication keywords:
ATPases Associated with Diverse Cellular ActivitiesEscherichia coli ProteinsPolyaminesMolecular ChaperonesProtein FoldingSingle Molecule ImagingProteasome Endopeptidase ComplexSaccharomyces cerevisiaeEndopeptidase ClpOrnithine DecarboxylaseProteolysisCysteine EndopeptidasesAdenosine TriphosphatasesUbiquitinMultienzyme Complexes

• Liver cancer multiomics reveals diverse protein kinase A disruptions convergently produce fibrolamellar hepatocellular carcinoma.
  Nature communications 2024 Requena D, Medico JA, Soto-Ugaldi LF, Shirani M, Saltsman JA, Torbenson MS, Coffino P, Simon SM
• Increased Protein Kinase A Activity Induces Fibrolamellar Hepatocellular Carcinoma Features Independent of DNAJB1.
  Cancer research 2024 Shirani M, Levin S, Shebl B, Requena D, Finkelstein TM, Johnson DS, Ng D, Lalazar G, Heissel S, Hojrup P, Molina H, de Jong YP, Rice CM, Singhi AD, Torbenson MS, Coffino P, Lyons B, Simon SM
• Targeted Degradation of Protein Kinase A via a Stapled Peptide PROTAC.
  ACS chemical biology 2024 Whittaker MK, Bendzunas GN, Shirani M, LeClair TJ, Shebl B, Dill TC, Coffino P, Simon SM, Kennedy EJ
• Disruption of proteome by an oncogenic fusion kinase alters metabolism in fibrolamellar hepatocellular carcinoma.
  Science advances 2023 Levin SN, Tomasini MD, Knox J, Shirani M, Shebl B, Requena D, Clark J, Heissel S, Alwaseem H, Surjan R, Lahasky R, Molina H, Torbenson MS, Lyons B, Migler RD, Coffino P, Simon SM
• Targeting BCL-XL in fibrolamellar hepatocellular carcinoma.
  JCI insight 2022 Shebl B, Ng D, Lalazar G, Rosemore C, Finkelstein TM, Migler RD, Zheng G, Zhang P, Jiang CS, Qureshi A, Vaughan R, Yarchoan M, de Jong YP, Rice CM, Coffino P, Ortiz MV, Zhou D, Simon SM

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• Single molecule microscopy reveals diverse actions of substrate sequences that impair ClpX AAA+ ATPase function.
  The Journal of biological chemistry 2022 Wang X, Simon SM, Coffino P
• Allostery Modulates Interactions between Proteasome Core Particles and Regulatory Particles.
  Biomolecules 2022 Coffino P, Cheng Y
• Identification of Novel Therapeutic Targets for Fibrolamellar Carcinoma Using Patient-Derived Xenografts and Direct-from-Patient Screening.
  Cancer discovery 2021 Lalazar G, Requena D, Ramos-Espiritu L, Ng D, Bhola PD, de Jong YP, Wang R, Narayan NJC, Shebl B, Levin S, Michailidis E, Kabbani M, Vercauteren KOA, Hurley AM, Farber BA, Hammond WJ, Saltsman JA, …
• Allosteric coupling between α-rings of the 20S proteasome.
  Nature communications 2020 Yu Z, Yu Y, Wang F, Myasnikov AG, Coffino P, Cheng Y
• Slippery substrates impair ATP-dependent protease function by slowing unfolding.
  The Journal of biological chemistry 2014 Coffino P, Too PH, Erales J
• Ubiquitin-independent proteasomal degradation.
  Biochimica et biophysica acta 2013 Erales J, Coffino P
• Reconfiguration of the proteasome during chaperone-mediated assembly.
  Nature 2013 Park S, Li X, Kim HM, Singh CR, Tian G, Hoyt MA, Lovell S, Battaile KP, Zolkiewski M, Coffino P, Roelofs J, Cheng Y, Finley D
• Slippery substrates impair function of a bacterial protease ATPase by unbalancing translocation versus exit.
  The Journal of biological chemistry 2013 Too PH, Erales J, Simen JD, Marjanovic A, Coffino P
• Ubiquitin proteasome system in stress and disease.
  Biochemistry research international 2012 Karpov D, Glickman MH, Bar-Nun S, Coffino P
• Functional asymmetries of proteasome translocase pore.
  The Journal of biological chemistry 2012 Erales J, Hoyt MA, Troll F, Coffino P
• Dependence of proteasome processing rate on substrate unfolding.
  The Journal of biological chemistry 2011 Henderson A, Erales J, Hoyt MA, Coffino P
• Ordering an engagement ring.
  Molecular cell 2010 Hoyt MA, Coffino P
• A genetic screen for Saccharomyces cerevisiae mutants affecting proteasome function, using a ubiquitin-independent substrate.
  Yeast (Chichester, England) 2008 Hoyt MA, McDonough S, Pimpl SA, Scheel H, Hofmann K, Coffino P
• Structural elements of the ubiquitin-independent proteasome degron of ornithine decarboxylase.
  The Biochemical journal 2008 Takeuchi J, Chen H, Hoyt MA, Coffino P
• Proteasome substrate degradation requires association plus extended peptide.
  The EMBO journal 2006 Takeuchi J, Chen H, Coffino P
• The cytoplasmic Hsp70 chaperone machinery subjects misfolded and endoplasmic reticulum import-incompetent proteins to degradation via the ubiquitin-proteasome system.
  Molecular biology of the cell 2006 Park SH, Bolender N, Eisele F, Kostova Z, Takeuchi J, Coffino P, Wolf DH
• Glycine-alanine repeats impair proper substrate unfolding by the proteasome.
  The EMBO journal 2006 Hoyt MA, Zich J, Takeuchi J, Zhang M, Govaerts C, Coffino P
• Probing the ubiquitin/proteasome system with ornithine decarboxylase, a ubiquitin-independent substrate.
  Methods in enzymology 2005 Hoyt MA, Zhang M, Coffino P
• Varshavsky's contributions.
  Science (New York, N.Y.) 2004 Baumeister W, Bachmair A, Chau V, Cohen R, Coffino P, Demartino G, Deshaies R, Dohmen J, Emr S, Finley D, Hampton R, Hill C, Hochstrasser M, Huber R, Jackson P, Jentsch S, Johnson E, Kwon YT, Pagano M…
• Ubistatins inhibit proteasome-dependent degradation by binding the ubiquitin chain.
  Science (New York, N.Y.) 2004 Verma R, Peters NR, D'Onofrio M, Tochtrop GP, Sakamoto KM, Varadan R, Zhang M, Coffino P, Fushman D, Deshaies RJ, King RW
• Development of a method for screening short-lived proteins using green fluorescent protein.
  Genome biology 2004 Jiang X, Coffino P, Li X
• Ubiquitin-free routes into the proteasome.
  Cellular and molecular life sciences : CMLS 2004 Hoyt MA, Coffino P
• Proteasomes begin ornithine decarboxylase digestion at the C terminus.
  The Journal of biological chemistry 2004 Zhang M, MacDonald AI, Hoyt MA, Coffino P
• Repeat sequence of Epstein-Barr virus-encoded nuclear antigen 1 protein interrupts proteasome substrate processing.
  The Journal of biological chemistry 2003 Zhang M, Coffino P
• Determinants of proteasome recognition of ornithine decarboxylase, a ubiquitin-independent substrate.
  The EMBO journal 2003 Zhang M, Pickart CM, Coffino P
• Transcriptional regulation of the ornithine decarboxylase gene by c-Myc/Max/Mad network and retinoblastoma protein interacting with c-Myc.
  The international journal of biochemistry & cell biology 2003 Auvinen M, Järvinen K, Hotti A, Okkeri J, Laitinen J, Jänne OA, Coffino P, Bergman M, Andersson LC, Alitalo K, Hölttä E
• Ubiquitin-independent mechanisms of mouse ornithine decarboxylase degradation are conserved between mammalian and fungal cells.
  The Journal of biological chemistry 2003 Hoyt MA, Zhang M, Coffino P
• Structural elements of antizymes 1 and 2 are required for proteasomal degradation of ornithine decarboxylase.
  The Journal of biological chemistry 2002 Chen H, MacDonald A, Coffino P
• An easily dissociated 26 S proteasome catalyzes an essential ubiquitin-mediated protein degradation pathway in Trypanosoma brucei.
  The Journal of biological chemistry 2002 Li Z, Zou CB, Yao Y, Hoyt MA, McDonough S, Mackey ZB, Coffino P, Wang CC
• Antizyme, a mediator of ubiquitin-independent proteasomal degradation.
  Biochimie 2001 Coffino P
• Regulation of cellular polyamines by antizyme.
  Nature reviews. Molecular cell biology 2001 Coffino P
• A homolog of mammalian antizyme is present in fission yeast Schizosaccharomyces pombe but not detected in budding yeast Saccharomyces cerevisiae.
  Bioinformatics (Oxford, England) 2000 Zhu C, Karplus K, Grate L, Coffino P
• Polyamines in spermiogenesis: not now, darling.
  Proceedings of the National Academy of Sciences of the United States of America 2000 Coffino P
• alpha5 subunit in Trypanosoma brucei proteasome can self-assemble to form a cylinder of four stacked heptamer rings.
  The Biochemical journal 1999 Yao Y, Toth CR, Huang L, Wong ML, Dias P, Burlingame AL, Coffino P, Wang CC
• Antizyme2 is a negative regulator of ornithine decarboxylase and polyamine transport.
  The Journal of biological chemistry 1999 Zhu C, Lang DW, Coffino P
• Regulated degradation of yeast ornithine decarboxylase.
  The Journal of biological chemistry 1999 Toth C, Coffino P
• Structure of mammalian ornithine decarboxylase at 1.6 A resolution: stereochemical implications of PLP-dependent amino acid decarboxylases.
  Structure (London, England : 1993) 1999 Kern AD, Oliveira MA, Coffino P, Hackert ML
• Developmental effect of polyamine depletion in Caenorhabditis elegans.
  The Biochemical journal 1998 MacRae M, Kramer DL, Coffino P
• High-risk human papillomavirus E6 protein has two distinct binding sites within p53, of which only one determines degradation.
  Journal of virology 1996 Li X, Coffino P
• Identification of a region of p53 that confers lability.
  The Journal of biological chemistry 1996 Li X, Coffino P
• The N terminus of antizyme promotes degradation of heterologous proteins.
  The Journal of biological chemistry 1996 Li X, Stebbins B, Hoffman L, Pratt G, Rechsteiner M, Coffino P
• Crystallization of a mammalian ornithine decarboxylase.
  Proteins 1996 Kern A, Oliveira MA, Chang NL, Ernst SR, Carroll DW, Momany C, Minard K, Coffino P, Hackert ML
• The ornithine decarboxylase gene of Caenorhabditis elegans: cloning, mapping and mutagenesis.
  Genetics 1995 Macrae M, Plasterk RH, Coffino P
• Rat antizyme inhibits the activity but does not promote the degradation of mouse ornithine decarboxylase in Trypanosoma brucei.
  The Journal of biological chemistry 1995 Hua SB, Li X, Coffino P, Wang CC
• Degradation of ornithine decarboxylase by the mammalian and yeast 26S proteasome complexes requires all the components of the protease.
  European journal of biochemistry 1995 Elias S, Bercovich B, Kahana C, Coffino P, Fischer M, Hilt W, Wolf DH, Ciechanover A
• Distinct domains of antizyme required for binding and proteolysis of ornithine decarboxylase.
  Molecular and cellular biology 1994 Li X, Coffino P
• Multiple active conformers of mouse ornithine decarboxylase.
  The Biochemical journal 1993 Tsirka SE, Turck CW, Coffino P
• Degradation of ornithine decarboxylase: exposure of the C-terminal target by a polyamine-inducible inhibitory protein.
  Molecular and cellular biology 1993 Li X, Coffino P
• Dominant negative mutants of ornithine decarboxylase.
  The Journal of biological chemistry 1992 Tsirka S, Coffino P
• Regulated degradation of ornithine decarboxylase requires interaction with the polyamine-inducible protein antizyme.
  Molecular and cellular biology 1992 Li X, Coffino P
• Role of ornithine decarboxylase suppression and polyamine depletion in the antiproliferative activity of polyamine analogs.
  Molecular pharmacology 1992 Ghoda L, Basu HS, Porter CW, Marton LJ, Coffino P
• Sequestered end products and enzyme regulation: the case of ornithine decarboxylase.
  Microbiological reviews 1992 Davis RH, Morris DR, Coffino P
• Structural elements of ornithine decarboxylase required for intracellular degradation and polyamine-dependent regulation.
  Molecular and cellular biology 1992 Ghoda L, Sidney D, Macrae M, Coffino P
• Expression and post-transcriptional regulation of ornithine decarboxylase during early Xenopus development.
  European journal of biochemistry 1991 Osborne HB, Duval C, Ghoda L, Omilli F, Bassez T, Coffino P
• Killer polyamines?
  Journal of cellular biochemistry 1991 Coffino P, Poznanski A
• Ornithine decarboxylase of African trypanosomes.
  Biochemical Society transactions 1990 Ghoda L, Wang CC, Coffino P
• Trypanosome ornithine decarboxylase is stable because it lacks sequences found in the carboxyl terminus of the mouse enzyme which target the latter for intracellular degradation.
  The Journal of biological chemistry 1990 Ghoda L, Phillips MA, Bass KE, Wang CC, Coffino P
• Regulation of mouse ornithine decarboxylase activity by cell growth, serum and tetradecanoyl phorbol acetate is governed primarily by sequences within the coding region of the gene.
  Nucleic acids research 1989 van Daalen Wetters T, Brabant M, Coffino P
• Polyamine-mediated regulation of mouse ornithine decarboxylase is posttranslational.
  Molecular and cellular biology 1989 van Daalen Wetters T, Macrae M, Brabant M, Sittler A, Coffino P
• Prevention of rapid intracellular degradation of ODC by a carboxyl-terminal truncation.
  Science (New York, N.Y.) 1989 Ghoda L, van Daalen Wetters T, Macrae M, Ascherman D, Coffino P
• Trypanosoma brucei ornithine decarboxylase: enzyme purification, characterization, and expression in Escherichia coli.
  The Journal of biological chemistry 1988 Phillips MA, Coffino P, Wang CC
• Probable cloning artefacts previously interpreted as unusual leader sequences of rodent ornithine decarboxylase mRNAs--a cautionary tale.
  Gene 1988 Coffino P
• Mouse ornithine decarboxylase gene: cloning, structure, and expression.
  Proceedings of the National Academy of Sciences of the United States of America 1988 Brabant M, McConlogue L, van Daalen Wetters T, Coffino P
• Nucleotide sequence of the mouse ornithine decarboxylase gene.
  Nucleic acids research 1988 Coffino P, Chen EL
• A functional mouse ornithine decarboxylase gene (Odc) maps to chromosome 12: further evidence of homoeology between mouse chromosome 12 and the short arm of human chromosome 2.
  Cytogenetics and cell genetics 1988 Cox DR, Trouillot T, Ashley PL, Brabant M, Coffino P
• Cloning and sequencing of the ornithine decarboxylase gene from Trypanosoma brucei. Implications for enzyme turnover and selective difluoromethylornithine inhibition.
  The Journal of biological chemistry 1987 Phillips MA, Coffino P, Wang CC
• Complementation of a polyamine-deficient Escherichia coli mutant by expression of mouse ornithine decarboxylase.
  Molecular and cellular biology 1987 Macrae M, Coffino P
• Multiple mechanisms are responsible for altered expression of ornithine decarboxylase in overproducing variant cells.
  Molecular and cellular biology 1986 McConlogue L, Dana SL, Coffino P
• Nerve growth factor rapidly induces ornithine decarboxylase mRNA in PC12 rat pheochromocytoma cells.
  Proceedings of the National Academy of Sciences of the United States of America 1985 Feinstein SC, Dana SL, McConlogue L, Shooter EM, Coffino P
• Mouse ornithine decarboxylase. Complete amino acid sequence deduced from cDNA.
  The Journal of biological chemistry 1985 Gupta M, Coffino P
• Molecular cloning and expression of the mouse ornithine decarboxylase gene.
  Proceedings of the National Academy of Sciences of the United States of America 1984 McConlogue L, Gupta M, Wu L, Coffino P
• A mouse lymphoma cell mutant whose major protein product is ornithine decarboxylase.
  The Journal of biological chemistry 1983 McConlogue L, Coffino P
• Ornithine decarboxylase in difluoromethylornithine-resistant mouse lymphoma cells. Two-dimensional gel analysis of synthesis and turnover.
  The Journal of biological chemistry 1983 McConlogue L, Coffino P
• Regulation of phosphodiesterase and ornithine decarboxylase by cAMP is cell cycle independent.
  Journal of cellular physiology 1979 Kaiser N, Bourne HR, Insel PA, Coffino P