Key Research Articles

EMSY inhibits homologous recombination repair and the interferon response promoting lung cancer immune evasion. 

Marzio A., Kurz E., Sahni J., Di Feo G., Puccini J., Jiang S., Hirsch C., Arbini A., Wu W., Pass H., Bar-Sagi D., Papagiannakopulos T., and Pagano M.

Cell, In press 2022.

 

CRL4-AMBRA1 is a master regulator of D-type cyclins.

Simoneschi D., Róna G., Zhou N., Jeong Y.T., Jiang S., Milletti G., Arbini A., O’sullivan A., Wang A., Nithikasem S., Keegan S., Siu Y., Cianfanelli V., Maiani E., Nazio F., Cecconi F., Boccalatte F., Fenyo D., Jones D., Busino L., and Pagano M.

Nature 592:789-793, 2021. (See also related N&V, NCI, Behind the Paper, Research Highlight, F1000, and In the News)

The NSP14/NSP10 RNA Repair Complex as a Pan-coronavirus Therapeutic Target. 

Rona G., Zeke A., Miwatani-Minter B., de Vries M., Kaur R., Schinlever A., Garcia S., Goldberg H., Wang H., Hinds T., Bailly F., Zheng N., Desmaële D., Landau N., Dittmann M., and Pagano M.

Cell Death & Differentiation, 29: 2021.  (See also related N&V)

Loss of FBXO31-mediated degradation of DUSP6 dysregulates ERK and PI3K-AKT signaling and promotes prostate tumorigenesis.

Duan S., Moro L., Qu R., Simoneschi D., Cho H., Jiang S., Zhao H., Chang Q., de Stanchina E., Arbini A., and Pagano M.

Cell Reports, 37:109870, 2021.

Epigenetic silencing of the ubiquitin ligase subunit FBXL7 impairs c-SRC degradation and promotes epithelial-to-mesenchymal transition and metastasis.

Moro L., Simoneschi D., Kurz E., Arbini A., Jiang S., Guaragnella N., Giannattasio S., Wang W., Chen Y.A., Pires G., Dang A., Hernandez E., Kapur P., Mishra A., Tsirigos A., Miller G., Hsieh J., and Pagano M.

Nature Cell Biol 22:1130-1142, 2020. (See also related N&V)

 

PHOTACs Enable Optical Control of Protein Degradation.

Reynders M., Matsuura B., Bérouti M., Simoneschi D., Marzio A., Pagano M.*, and Tauner D.*

Science Advances 6:eaay5064, 2020. (See also related Spotlight)

 

Nrf2 activation promotes lung cancer metastasis by inhibiting the degradation of Bach1.

Lignitto L., LeBoeuf S., Homer H., Jiang S., Askenazi M., Karakousi T., Pass H., Bhutkar A., Tsirigos A., Ueberheide B., Sayin V., Papagiannakopulos T, and Pagano M.

Cell 178:316-329, 2019.  (See also related Preview, N&V, F1000, and In the News)

 

Cyclin F controls cell cycle transcriptional outputs by directing the degradation of the three activator E2Fs.

Clijsters L., Hoencamp C., Calis J., Marzio A, Handgraaf S., Cuitino M., Rosenberg B., Leone G., and Pagano M.

Mol Cell 74:1264-1277, 2019.  (See also related N&V and related review)

 

GGTase3 is a Newly Identified Geranylgeranyltransferase Targeting a Ubiquitin Ligase.

Kuchay S., Wang H., Marzio A., Jain K., Homer H., Fehrenbacher N., Philpps M., Zheng N., and Pagano M.

Nature Str & Mol Biol 26:628-636, 2019(See also related Editors' Choice and N&V)

 

Cryptochromes-mediated inhibition of the CRL4-Cop1-complex assembly defines an evolutionary conserved signaling mechanism.

Rizzini L., Levine D., Perelis M., Bass J., Peek C., and Pagano M.

Current Biol 29:1954-1962, 2019.   (See also related Commentary)

 

The F-box domain-dependent activity of EMI1 regulates PARPi sensitivity in triple negative breast cancers.

Marzio A., Puccini J., Kwon Y., Maverakis N., Arbini A., Sung P., Bar-Sagi D., and Pagano M.

Mol Cell 73:224-237, 2019(See also related Preview and F1000)

The ULK1-FBXW5-SEC23B nexus controls autophagy.

Jeong Y., Simoneschi D., Keegan S., Melville D., Adler. N., Saraf A., Florens L., Washburn M., Casavotto C., Fenyo D., Cuervo A., Rossi M., and Pagano M.

eLife 7:e42253, 2018(See also related Insight)

 

NS5A promotes constitutive degradation of IP3R3 to counteract apoptosis induced by hepatitis C virus.

Kuchay S., Saeed M., Giorgi C., Li J., Hoffmann H., Pinton P., Rice C., and Pagano M.

Cell Reports 25:833-840 2018.

 

PARP1-dependent recruitment of the FBXL10-RNF68-RNF2 ubiquitin ligase to sites of DNA damage controls H2A.Z loading.

Rona G., Roberti D., Yin Y., Pagan J., Homer. H., Sassani E., Zeke A., Busino L., Rothenberg E., and Pagano M.

eLife 7:e38771, 2018.

 

PTEN counteracts FBXL2 to promote IP3R3- and Ca2+-mediated apoptosis limiting tumor growth.

Kuchay S., Giorgi C., Simoneschi D., Pagan J., Missiroli S., Saraf A., Florens L., Washburn M., Collazo A., Castillo M., Cordon-Cardo C., Sebti S., Pinton P., and Pagano M.

Nature 546:554-558, 2017. (See also related News & Views, News & Thoughts, and In the News)

 

The TDH-GCN5L1-Fbxo15-KBP axis limits mitochondrial biogenesis in mouse embryonic stem cells.

Donato V., Bonora, M. Simoneschi D., Sartini D., Kudo Y., Saraf A., Florens L., Washburn M., Stadtfeld M., Pinton, P., and Pagano M.

Nature Cell Biol 19:341-351, 2017. (See also related News & Commentary and related Review)

 

FEM1 proteins are ancient regulators of SLBP degradation.

Dankert J., Pagan J., Starostina N., Kipreos E., and Pagano M.

Cell Cycle 16:556-564, 2017.

 

Cyclin F-mediated degradation of SLBP limits H2A.X accumulation and apoptosis upon genotoxic stress in G2.

Dankert J., Rona G., Clijsters L., Geter P., Skaar J., Bermudez K., Sassani E., Fenyo D., Ueberheide B., Schneider R., and Pagano M.

Mol Cell 64:507-519, 2016 (See also related Review and News & Views)

Degradation of Cep68 and PCNT cleavage mediate Cep215 removal from the PCM to allow centriole separation, disengagement

and licensing.

Pagan J., Marzio A., Jones M., Saraf A., Jallepalli P., Florens L., Washburn M., and Pagano M.

Nature Cell Biol 17:31-43, 2015(See also related News & Views)

 

TIMELESS forms a complex with PARP1 distinct from its complex with TIPIN and plays a role in the DNA Damage Response.

Young L.M., Marzio A., Perez-Duran P., Reid D., Meredith D., Roberti, D. Star A., Rothenberg E., Ueberheide B., and Pagano M.

Cell Reports 13:451-459, 2015.

 

The Integrator complexes regulates processing-coupled termination of transcription at diverse classes of gene targets.

Skaar J., Ferris A., Wu X., Saraf A., Khanna K., Florens L., Washburn M., Hughes S. and Pagano M.

Cell Res 25:288-305, 2015 (See also related Mini-Review)

 

FBXL2- and PTPL1-mediated degradation of p85β controls PI3K activity

Kuchay S., Duan S., Schenkein E., Peschiaroli A., Saraf A., Florens L., Washburn M., and Pagano M.

Nature Cell Biol 15:472-480, 2013.

 

Regulation of the CRL4Cdt2 ubiquitin ligase and cell cycle exit by the SCFFbxo11 ubiquitin ligase.

Rossi M., Duan S., Jeong Y., Horn M., Saraf A., Florens L., Washburn M., Antebi A., and Pagano M.

Mol Cell 49:1159-1166, 2013.

 

FBH1 promotes DNA double strand breakage and apopotosis in response to DNA replication stress.

Jeong Y., Rossi M., Cermak L., Saraf A., Florens L., Washburn M., Sung. P, Schildkraut C., and Pagano M.

J of Cell Biol 200:141-149, 2013.

 

FBH1 is deregulated in melanomas and protects melanocytes from transformation.

Jeong Y., Cermak L., GuiJarro M., Hernando E., and Pagano M.

Cell Cycle 12:1128-1132, 2013.

Cyclin F-dependent degradation of Ribonucleotide Reductase M2 controls genome stability and DNA repair.

D'Angiolella V., Donato V., Jeong Y., Forrester F., Kudo, Y., Pellacani C., Saraf A., Florens L., Washburn M., and Pagano M.

Cell 149:1023-1034, 2012.

 

Fbxw7α- and GSK3-mediated degradation of p100 is a pro-survival mechanism in multiple myeloma.

Busino L., Millman S., L. Scotto, Kyratsous C., Basrur V., Hoffmann A., O'Connor O., Elenitoba-Johnson K. S., and Pagano M.

Nature Cell Biol, 14:375-385, 2012.

 

FBXO11 targets BCL6 for degradation and is inactivated in diffuse large B-cell lymphomas.

Duan S., L. Cermak, J. Pagan, M. Rossi, C. Martinengo , P. DiCelle, B. Chapyuy, M. Shipp, R. Chiarle, and Pagano M.

Nature 481:90-93, 2012.

 

mTOR generates an auto-amplification loop by triggering the βTrCP- and Ck1α-dependent degradation of DEPTOR.

Duan S., Skaar J.R., Tosci A., Kanarek N., Ben-Neriah Y., and Pagano M.

Mol Cell 44;317-324, 2011.

 

APC/C- and Mad2-mediated degradation of Cdc20 during spindle checkpoint activation.

Ge S., J. Skaar, and Pagano M.

Cell Cycle 8:167-171, 2011.

 

SCFCyclin F controls centrosome homeostasis and mitotic fidelity via CP110 degradation.

D’Angiolella, V. Donato, S. Vijayakumar, A. Saraf, L. Florens, M. Washburn, B. Dynlacht, and Pagano M.

Nature 466:138-142, 2010.

 

INTS3 controls the hSSB1-mediated DNA damage response.

Skaar J., D. Richard, A. Tosci, A. Saraf, E. Bolderson, L. Florens, M. Washburn, K. Khanna, and Pagano M.

J of Cell Biol 187:25-32, 2009.

 

βTrCP- and Rsk1/2-mediated degradation of BimEL inhibits apoptosis.

Dehan E., F. Bassermann, D. Guardavaccaro, G. Vasiliver-Shamis, M. Cohen, K. Lowes, M. Dustin, D. Huang, J. Taunton, and Pagano M.

Mol Cell 33:109-111, 2009.

The Cdc14B-Cdh1-Plk1 axis controls the G2 DNA damage response checkpoint.

Bassermann F., D. Frescas, D. Guardavaccaro, L. Busino, A. Peschiaroli, and Pagano M.

Cell 134:256-267, 2008.

 

Control of chromosome stability by the βTRCP-REST-MAD2 axis.

Guardavaccaro D., D. Frescas, N. Dorrello, A. Peschiaroli, A. Multani, T. Cardozo, A. Lasorela, A. Iavarone, S. Chang, E. Hernando, and Pagano M.

Nature 452:365-369, 2008.

 

The histone demethylase JHDM1B/FBXL10 is a nucleolar protein that represses transcription of ribosomal RNA genes.

Frescas D., D. Guardavaccaro, F. Bassermann, R. Koyama-Nasu and M. Pagano.

Nature 450:309-313, 2007.

 

SCFFbxl3 Controls the Oscillation of the Circadian Clock by Directing the Degradation of Cryptochrome Proteins.

Busino L., F. Bassermann, A. Maiolica, C Lee, S. Godinho, P. Nolan, G. Draetta and Pagano M.

Science 316:900-904, 2007.

 

APC/CCdc20 controls the ubiquitin-mediated degradation of p21 in prometaphase.

Amador V., S. Ge, P.G. Santamaria, D. Guardavaccaro and Pagano M.

Mol Cell 27:462-473, 2007.

 

S6K1- and βTRCP-mediated degradation of PDCD4 promotes protein translation and cell growth.

Dorrello N. V., A. Peschiaroli, D. Guardavaccaro, N. H. Colburn, N. E. Sherman and Pagano M.

Science 314:467-471, 2006.

 

SCFβTRCP-mediated degradation of Claspin regulates recovery from the DNA replication checkpoint response.

Peschiaroli A., N. V. Dorrello, D. Guardavaccaro, M. Venere, T. Halazonetis, N. Sherman and Pagano M..

Mol Cell 23:319-329, 2006.

 

Role of F-box protein βTrcp1 in mammary gland development and tumorigenesis.

Kudo Y., D. Guardavaccaro, P. Santamaria, R. Nasu, E. Latres, R. Bronson, L. Yamasaki and Pagano M.

Mol Cell Biol 24:8184-8194, 2004.

Control of the SCFSkp2-Cks1 ubiquitin ligase by the APC/CCdh1 ubiquitin ligase.

Bashir T., V. Dorrello, V. Amador, D. Guardavaccaro and Pagano M.

Nature 248:190-193, 2004.

 

Proteasome-mediated degradation of p21 via N-terminal ubiquitinylation.

Bloom J., V. Amador, F. Bartolini, G. DeMartino and Pagano M.

Cell 115:71-82, 2003.

 

Control of meiotic and mitotic progression by the F-box protein βTrcp1 in vivo.

Guardavaccaro D., Y. Kudo, J. Boulaire, M. Barchi, L. Busino, M. Donzelli, F. Margottin, P. Jackson, Yamasaki L. and Pagano M.

Dev. Cell 4: 799-812, 2003.

 

Oncogenic role of the ubiquitin ligase subunit Skp2 in human breast cancer.

Signoretti S., L. Dimarcotullio, A. Richardson, S. Ramaswamy, B. Isaac, M. Rue, F. Monti, M. Loda and Pagano M.

J of Clinical Investigation 110:633-641, 2002.

 

Role of the F-box protein Skp2 in adhesion-dependent cell cycle progression.

Carrano A. C. and Pagano M..

J of Cell Biology 153: 1381-1389, 2001.

 

Role of the F-box protein Skp2 in lymphomagenesis.

Latres E., R. Chiarle, B. Schulman, N. Pavletich, A. Pellicer, G. Inghirani and Pagano M.

Proc Natl Acad Sci USA 98: 2515-2520, 2001.

 

Identification of a family of human F-box proteins.

Cenciarelli C., D. S. Chiaur, D. Guardavaccaro, W. Parks, M. Vidal, and Pagano M.

Current Biology 9: 1177-1179, 1999.

 

Skp2 is required for the ubiquitin-mediated degradation of the Cdk-inhibitor p27.

Carrano A. C., E. Eytan, A. Hershko, and Pagano M.

Nature Cell Biol 1: 193-199, 1999.

 

Ubiquitination of p27 is regulated by Cdk-dependent phosphorylation and trimeric complex formation.

Montagnoli A., F. Fiore, E. Eytan, A. C. Carrano, G. Draetta, A. Hershko, and Pagano M.

Genes & Development 13: 1181-1189, 1999.

The human F-box protein β-Trcp associates with the Cul1/Skp1 complex and regulates the stability of b-catenin.

Latres E., D. S. Chiaur, and Pagano M.

Oncogene 18: 849-854, 1999.

 

Increased proteasome-dependent degradation of the CDK inhibitor p27 in aggressive colorectal carcinomas.

Loda M., B. Cukon, S. Tam, P. Lavin, M. Fiorentino, G. Draetta, J. Jessup, and Pagano M.

Nature Med 3: 231-234, 1997.

Human Cyclin E, a nuclear protein essential for the G1 to S phase transition.

Ohtsubo M., A. Theodoras, J. Schumacher, J. Roberts, and Pagano M.

Mol Cell Biol 15: 2612-2624, 1995.

 

Role of the Ubiquitin-Proteasome pathway in regulating abundance of the CDK inhibitor p27.

Pagano M., S. Tam, A. Theodoras, P. Beer, S. Delsal, V. Chu, R. Yew, G. Draetta, and M. Rolfe.

Science 269: 682-685, 1995.

 

Cyclin D1-mediated inhibition of repair and replicative DNA synthesis in human fibroblasts.

Pagano M., A. M. Theodoras, S. W. Tam, and G. Draetta.

Genes & Development 8: 1627-1639, 1994.

 

Regulation of the cell cycle by the Cdk2 protein kinase in cultured human fibroblasts.

Pagano M., R. Pepperkok, J. Lukas, V. Baldin, W. Ansorge, J. Bartek, and G. Draetta.

J of Cell Biology 121: 101- 111, 1993.

 

Binding of the human E2F transcription factor to the retinoblastoma protein but not Cyclin A is abolished in HPV 16-immortalized cells.

Pagano M., M. Dürst, S. Joswig, G. Draetta, and P. Jansen-Dürr.

Oncogene 7: 1681-1686, 1992.

 

Cyclin A is required at two points in the human cell cycle.

Pagano M., R. Pepperkok, F. Verde, W. Ansorge, and G. Draetta.

EMBO J 11: 961-972, 1992.

 

Association of Cdk2 kinase with the transcription factor E2F during S phase.

Pagano M., Draetta G., and Jansen-Dürr P.

Science 255: 1144-1147, 1992.