Michele Pagano, M.D.
May Ellen and Gerald Jay Ritter Professor of Oncology and Professor of Pathology
Leader of the Growth Control Program, NYU Cancer Institute
Experimental Pathology, Molecular Oncology, Pathobiology / Ubiquitin system, cell division cycle checkpoints, cancer
michele.pagano@nyumc.org, (212) 263 5332 , (212) 263 5129
Fax: (212) 263 5107
550 First Avenue, MSB 599, New York, NY 10016
Research and Clinical Interests
The mammalian SCF (Skp1/Cul1/F-box protein) ubiquitin ligases are critical for the attenuation/activation of many cellular functions. They control molecular machines by directing the proteolysis of important regulatory elements in a precise, rapid, and localized manner. We found that SCF regulates multiple and seemingly disparate cellular pathways: cell cycle, protein synthesis, ribosomal biogenesis, cell survival, DNA-damage checkpoints, the circadian clock, etc. We also study how this regulatory network is deregulated in cancer cells.
Selected Publications
Guardavaccaro D, Frescas D, Dorrello NV, Peschiaroli A, Multani A, Cardozo T, Lasorella A, Iavarone A, Chang S, Hernando E, Pagano M. Control of chromosome stability by the βTRCP-REST-MAD2 axis. Nature. 2008 Mar 20;452:365-9. Cited in Pubmed; PMID 18354482.
Frescas D, Guardavaccaro D, Bassermann F, Nasu R, Pagano M. JHDM1B/FBXL10 demethylates is a nucleolar protein that represses transcription of ribosomal RNA genes. Nature. 2007 Nov 8;450:309-13. Cited in Pubmed; PMID 17994099.
Amador V, Ge S, Santamaria P, Guardavaccaro D, Pagano M. APC/C(Cdc20) controls the ubiquitin-mediated degradation of p21 during mitosis. Mol Cell. 2007 Aug 3;27:462-73. Cited in Pubmed; PMID 17679094.
Busino L, Bassermann F, Maiolica A, Lee C, Godinho S, Nolan P, Draetta G, Pagano M. SCFFbxl3 Controls the Oscillation of the Circadian Clock by Directing the Degradation of Cryptochrome Proteins. Science. 2007 May 11;316:316:900–4. Epub 2007 Apr 26. Cited in Pubmed; PMID 17463251.
Dorrello NV, Peschiaroli A, Guardavaccaro D, Colburn N, Sherman N, Pagano M. S6K1- and ßTrcp-mediated degradation of PDCD4 promotes protein translation and cell growth. Science. 2006 Oct 20;314:467–71. Cited in Pubmed; PMID 17053147.
Peschiaroli A, Dorrello NV, Guardavaccaro D, Venere M, Halazonetis T, Sherman N, Pagano M. SCFbetaTrCP-mediated degradation of Claspin regulates recovery from the DNA replication checkpoint response. Mol Cell. 2006 Aug 4;23:319-29. Cited in Pubmed; PMID 16885022.
Bashir T, Dorrello NV, Amador V, Guardavaccaro D, Pagano M. Control of the SCF(Skp2-Cks1) ubiquitin ligase by the APC/C(Cdh1) ubiquitin ligase. Nature. 2004 Mar 11;428:190–3. Cited in Pubmed; PMID 15014502.
Bloom J, Amador V, Bartolini F, DeMartino G, Pagano M. Proteasome-mediated degradation of p21 via N-terminal ubiquitinylation. Cell. 2003 Oct 3;115:71–82. Cited in Pubmed; PMID 14532004.
Guardavaccaro D, Kudo Y, Boulaire J, Barchi M, Busino L, Donzelli M, Yamasaki L, Pagano M. Control of meiotic and mitotic progression by the F-box protein β-Trcp1 in vivo. Dev Cell. 2003;4:799-812. Cited in Pubmed; PMID 12791266.
Signoretti S, Dimarcotullio L, Richardson A, Ramaswamy S, Isaac B, Rue M, Monti F, Loda M, Pagano M. Oncogenic role of the ubiquitin ligase subunit Skp2 in human breast cancer. J Clin Invest. 2002 Sep;110:633-41. Cited in Pubmed; PMID 2208864.
Carrano AC, Pagano M. Role of the F-box protein Skp2 in adhesion-dependent cell cycle progression. J Cell Biol. 2001 Jun 25;153(7):1381–9. Cited in Pubmed; PMID 11425869.
Latres E, Chiarle R, Schulman B, Pavletich NP, Pellicer A, Inghirami G, Pagano M. Role of the F-box protein Skp2 in lymphomagenesis. Proc Natl Acad Sci U S A. 2001 Feb 27;98:2515-20. Epub 2001 Feb 20. Cited in Pubmed; PMID 11226270.
Cenciarelli C, Chiaur DS, Guardavaccaro D, Parks W, Vidal M, Pagano M. Identification of a family of human F-box proteins. Curr Biol. 1999 Oct 21;9:1177–9. Cited in Pubmed; PMID 10531035.
Carrano AC, Eytan E, Hershko A, Pagano M. Skp2 is required for the ubiquitin-mediated degradation of the Cdk-inhibitor p27. Nat Cell Biol. 1999 Aug;1:193-9. Cited in Pubmed; PMID 10559916.
Selected Books and Reviews
Frescas D, Pagano M. Deregulated proteolysis by the F-box proteins SKP2 and beta-TrCP: tipping the scales of cancer. Nature Rev Cancer. 2008 Jun;8(6):438-49. Cited in Pubmed; PMID 18500245. doi: doi:10.1038/nrc2396.
Santamaria P, Pagano M. The pRb-Cdh1-p27 autoamplifying network. Nature Cell Biol. 2007;9:137-138.
Pagano M. Control of the cell cycle by the ubiquitin system. In: AACR Education Book 1. Philadelphia: American Association for Cancer Research; 2006. pp. 162–5.
Bashir T, Pagano M. Aberrant ubiquitin-mediated proteolysis of cell cycle regulatory proteins and oncogenesis. Advances in Cancer Research. 2003;88:101-44.
Bashir T, Pagano M. Cdk1, the dominant sibling of Cdk2. Nature Cell Biol. 2005;8:779-781.
Yamasaki L, Pagano M. Cell cycle, proteolysis and cancer. Curr Op in Cell Biol. 2004;16:623-28.
Pagano M. Control of DNA synthesis and Mitosis by the Skp2-p27-Cdk1/2 axis. Mol Cell. 2004;14:414-16.
Bloom J, Pagano M. Experimental tests to definitively determine ubiquitylation of a substrate. Meth in Enzymol. 2005;399:249-66.
Dehan E, Pagano M. Skp2, the FoxO1 hunter. Cancer Cell. 2005;7:209-210.
Guardavaccaro D, Pagano M. Stabilizers and destabilizers controlling cell cycle oscillators. Mol Cell. 2006;22:1-4.
Jin J, Cardozo T, Lovering R, Elledge SJ, Pagano M, Harper JW. Systematic analysis and nomenclature of mammalian F-box proteins. Genes & Development. 2004;18:2573-80.
Cardozo T, Pagano M. The SCF ubiquitin ligase: insights into a molecular mechanism. Nature Rev Mol Cell Biol. 2004;5:739-53.
Pagano M, Jackson P. Wagging the Dogma: Tissue specific Cell Cycle Control in the Mouse Embryo. Cell. 2004;118:535-8.
Pagano M, Benmaamar R. When protein destruction runs amok, malignancy is on the loose. Cancer Cell. 2003;4:251-6.
Bloom J, Pagano M. Regulation of p27 degradation. In: Ciechanover AJ, Masucci MG, editors. The ubiquitin-proteasome proteolytic system. Singapore: World Scientific Publishing; 2002. pp. 141–62.
Organizational Associations
American Italian Cancer Foundation; Editorial Board: Journal of Biological Chemistry; Editorial Board: Cancer Research; Editorial Board: Bio Med Central Cell Biology; Editorial Board: Bio Med Cell Division; Faculty of 1000
Selected Awards
2006 NIH MERIT Award (CA76584)
2005 Ritter Chair of Oncology
2000 - 04 Irma T. Hirschl Scholar
1993 - 96 Human Frontiers Science Program Organization Research Fellow
1992 Post-doctoral Fellowship (European Molecular Biology Laboratory)
1990 - 91 Post-doctoral Fellowship (Commission of European Communities)
1987 - 89 Pre-doctoral Fellowship (Italian Association for Cancer Research)
