People

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

Kuchay, S., Duan. S., Schenkein E.,Peschiaroli A., Saraf A., Florens L., Washburn M., and Pagano M.. FBXL2- and PTPL1-mediated degradation of p110-free p85β regulatory subunit controls the PI(3)K signalling cascade. Nature Cell Biology. 2013 Apr 21;15:472-480. doi: 10.1038/ncb2731.

Rossi M., Duan S., Jeong Y., Horn M., Saraf A., Florens L., Washburn M., Antebi A., and Pagano M.. Regulation of the CRL4Cdt2 ubiquitin ligase and cell cycle exit by the SCFFbxo11 ubiquitin ligase.. Molecular Cell. 2013 Mar 28;49:1159-1166. doi: 10.1016/j.molcel.2013.02.004.

Jeong Y., Rossi M., Cermak L., Saraf A., Florens L., Washburn M., Sung P., Schildkraut C., and Pagano M. FBH1 promotes DNA double strand breakage and apopotosis in response to DNA replication stress.. Journal of Cell Biology. 2013 Jan 21;141-9:doi: 10.1083/jcb.201209002.

D’Angiolella V., Donato V., Jeong Y., Forester F., Kudo, Y., Pellacani C., Saraf A., Florens L., Washburn M., and Pagano M.. Cyclin F-dependent degradation of Ribonucleotide Reductase M2 controls genome stability and DNA repair. Cell. 2012 May;149:1023-34. doi: 10.1016/j.cell.2012.03.043. PMCID: 22632967.

Busino L., Millman S., L. Scotto, Kyratsous C., Basrur V., Hoffmann A., O’Connor O., Elenitoba-Johnson K. S., and Pagano M. Fbxw7a- and GSK3-mediated degradation of p100 is a pro-survival mechanism in multiple myeloma. Nature Cell Biol.. 2012 Mar;14:375-385. Cited in Pubmed; PMID 22388891. doi: 10.1038/ncb2463.

Duan S., L. Cermak, J. Pagan, M. Rossi, C. Martinengo , P. DiCelle, B. Chapyuy, M. Shipp, R. Chiarle, and Pagano M. FBXO11 targets BCL6 for degradation and is inactivated in diffuse large B-cell lymphomas. Nature. 2012;481:90-93. Cited in Pubmed; PMID 22113614. doi: 10.1038/nature10688. PMCID: PMC3344385.

Duan S, Skaar JR, Kuchay S, Toschi A, Kanarek N, Yinon BN, Pagano M. mTOR Generates an Auto-Amplification Loop by Triggering the βTrCP- and CK1α-Dependent Degradation of DEPTOR. Mol Cell. 2011 Oct 21;44(2):317-24. Cited in Pubmed; PMID 22017877. doi: 10.1016/j.molcel.2011.09.005.

Skaar JR, Richard DJ, Saraf A, Toschi A, Bolderson E, Florens L, Washburn MP, Khanna KK, Pagano M. INTS3 controls the hSSB1-mediated DNA damage response. J Cell Biol. 2009 Oct 5;187(1):25-32. Cited in Pubmed; PMID 19786574. doi: 10.1083/jcb.200907026. PMCID: PMC2762097.

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. doi: 10.1038/nature06641. PMCID: PMC2707768.

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. doi: 10.1038/nature06255.

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.

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.

Selected Reviews

Skaar J., Pagan K., and Pagano M.. Substrate recruitment by F-box proteins: mechanisms and targets for therapeutics. Nature Reviews Molecular Cell Biology. 2013 Jun;14:369-381. doi: 10.1038/nrm3582.

D'Angiovella V., Esencay M., and Pagano M.. A cyclin without CDKs, cyclin F controls genome stability through ubiquitin-mediated proteolysis. Trends in Cell Biology. 2013 Mar 23;3:135-40. doi: 10.1016/j.tcb.2012.10.011.

Basserman F., Eichner R., and Pagano M.. The ubiquitin proteasome system – Implications for cell cycle control and the targeted treatment of cancer. Biochim Biophys Acta.. 2013 Mar 1;Cited in Pubmed; PMID 23466868. doi: 10.1016/j.bbamcr.2013.02.028.

Busino L., Millman Scott E., and Pagano M.. SCF-Mediated Degradation of p100 (NF-κB2): Mechanisms and Relevance in Multiple Myeloma. Science Signaling. 2012 Dec 4;253:doi: 10.1126/scisignal.2003408.

Silverman J., Skaar J., and Pagano M.. SCF ubiquitin ligases in the maintenance of genome stability. Trends in Biomedical Sciences. 2012 Feb;37(2):66-73. Cited in Pubmed; PMID 22099186. doi: 10.1016/j.tibs.2011.10.004. PMCID: PMC3278546.

Pagan J, Pagano M. FBXW5 controls centrosome number. Nat Cell Biol. 2011 Aug 1;13(8):888-90. Cited in Pubmed; PMID 21808243. doi: 10.1038/ncb2312.

Millman SE, Pagano M. MCL1 meets its end during mitotic arrest. EMBO Rep. 2011 May 1;12(5):384-5. Cited in Pubmed; PMID 21475247. doi: 10.1038/embor.2011.62. PMCID: PMC3090028 [Available on 2012/5/1].

Millman SE., and Pagano M. . MCL1 meets its end during mitotic arrest. EMBO Reports. 2011 May 1;384-385. doi: 10.1038/embor.2011.62. PMCID: PMC3090028.

Skaar JR, Pagano M. Control of cell growth by the SCF and APC/C ubiquitin ligases. Curr Opin Cell Biol. 2009 Dec;21(6):816-24. Cited in Pubmed; PMID 19775879.

Skaar JR, D'Angiolella V, Pagan JK, Pagano M. SnapShot: F Box Proteins II. Cell. 2009 Jun 26;137(7):1358, 1358.e1. doi: 10.1016/j.cell.2009.05.040.

Skaar JR, Pagan JK, Pagano M. SnapShot: F box proteins I. Cell. 2009 Jun 12;137(6):1160-1160.e1. doi: 10.1016/j.cell.2009.05.039.

Pagano M. Tagged for cleansing. The Scientist. 2009;23:26-31.

Skaar JR, Pagano M. Cdh1: a master G0/G1 regulator. Nat Cell Biol. 2008 Jul;10(7):755-7. Cited in Pubmed; PMID 18591966. doi: 10.1038/ncb0708-755.

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.

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

2007 Multiple Myeloma Research Foundation Senior Award
2007 The Eunice and Irving Leopold lecture, University of Pennsylvania, PA
2007 The Interurban Clinical Club lecture, Albert Einstein College of Medicine, NY
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)

Additional Information

HHMI Pagano Homepage