Daniele Guardavaccaro

Daniele Guardavaccaro received his PhD from “Universita’ La Sapienza” in Rome and subsequently trained at the Institute of Neurobiology at the Italian National Research Council. In 1998 he moved to the New York University School of Medicine where he joined the laboratory of Michele Pagano and from 1999 to 2000 he was a visiting scientist in the laboratory of Lili Yamasaki at Columbia University in New York. During these years he studied the role of the ubiquitin-proteasome system in the cell division cycle. In 2008 he was appointed group leader at the Hubrecht Institute where he continues to study the functions of ubiquitin-dependent proteolysis in normal cells and how altered protein degradation by the ubiquitin-proteasome system contributes to the uncontrolled growth and proliferation typical of cancer cells.


Team membersGuardavaccaro

Zunamys Carrero


Alejandro Hortal Borowski


Ana Krotenberg


Laurensia Yuniati


Roberto Magliozzi


Ilona den Hartog


Daniele Guardavaccaro

Group leader

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Guardavaccaro: Ubiquitin-dependent degradation in signaling, development and disease

The ubiquitin-proteasome system controls molecular networks that underlie fundamental cellular processes such as cell cycle progression, differentiation and apoptosis. A large body of experimental and clinical data reveals that components of the ubiquitin system, and in particular ubiquitin ligases that provide substrate specificity, are often the target of cancer-related deregulation and are involved in oncogenic transformation and tumor progression. The main objective of our research is the elucidation of the molecular mechanisms by which aberrant functions of ubiquitin ligases contribute to oncogenesis. To this aim, we integrate classic biochemical methods, mass spectrometry-based high-throughput screens, cell biological approaches as well...

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Key publications

Control of Epithelial Cell Migration and Invasion by the IKKβ- and CK1α-Mediated Degradation of RAPGEF2.
Magliozzi R, Low TW, Weijts BGMW, Cheng T, Spanjaard E, Mohammed S, van Veen A, Ovaa H, de Rooij J, Zwartkruis FJT, Bos JL, de Bruin A, Heck AJR, Guardavaccaro D.
Dev Cell. 2013 Dec 9;27(5):574-85.


Coupled activation and degradation of eEF2K regulates protein synthesis in response to genotoxic stress.
Kruiswijk F, Yuniati L, Magliozzi R, Low TW, Lim R, Bolder R, Mohammed S, Proud CG, Heck AJR, Pagano M, and Guardavaccaro D.
Science Signaling. 2012 Jun 5;5(227):ra40.
See also: Perspective


Control of chromosome stability by the βTrCP-REST-Mad2 axis.
Guardavaccaro D, Frescas D, Dorrello NV, Peschiaroli A, Multani AS, Cardozo T, Lasorella A, Iavarone A, Chang S, Hernando E, Pagano M.
Nature. 2008 Mar 20;452(7185):365-9.


Degradation of Id2 by the anaphase-promoting complex couples cell cycle exit and axonal growth.
Lasorella A, Stegmüller J, Guardavaccaro D, Liu G, Carro MS, Rothschild G, de la Torre-Ubieta L, Pagano M, Bonni A, Iavarone A.
Nature. 2006 Jul 27;442(7101):471-4.


Control of meiotic and mitotic progression by the F-box protein βTrCP1 in vivo.
Guardavaccaro D, Kudo Y, Boulaire J, Barchi M, Busino L, Donzelli M, Margottin-Goguet F, Jackson PK, Yamasaki L, Pagano M.
Dev Cell. 2003 Jun;4(6):799-812.

Selected publications

Tessadori, F., Noël, E.S., Rens, E.G., Magliozzi, R., Evers-van Gogh, I.J.A., Guardavaccaro, D., Merks, R.M.H., Bakkers, J. Nodal signalling range is regulated by proprotein convertase-mediated secretion.
Dev Cell. 2015 Feb 11. pii: S1534-5807(14)00835-1.

Low, T.Y., Peng, M., Magliozzi, R., Mohammed, S., Guardavaccaro, D., Heck, A.J. A systems-wide screen identifies substrates of the SCFβTrCP ubiquitin ligase.
Science Signaling 7(356):rs8, 2014

Kim, J., D’Annibale, S., Magliozzi, R., Low, T.Y., Jansen, P., Shaltiel, I.A., Mohammed, S., Heck, A.J., Medema, R.H., Guardavaccaro, D. USP17- and SCFβTrCP-regulated degradation of DEC1 controls the DNA damage response.
Mol Cell Biol. 34(22):4177-85, 2014.

Magliozzi, R., Kim, J., Low, T.Y., Heck, A.J., Guardavaccaro, D. Degradation of Tiam1 by casein kinase 1 and the SCFβTrCP ubiquitin ligase controls the duration of mTOR-S6K signaling.
J Biol Chem. 289(40):27400-9, 2014.

D’Annibale, S., Kim, J., Magliozzi, R., Low, T.Y., Mohammed, S., Heck, A.J., Guardavaccaro, D. Proteasome-dependent degradation of Transcription Factor AP4 (TFAP4) controls mitotic division.
J Biol Chem 289(11):7730-7, 2014

Magliozzi, R., Low, T.W., Weijts, B.G.M.W., Cheng, T., Spanjaard, E., Mohammed, S., van Veen, A., Ovaa, H., de Rooij, J., Zwartkruis, F.J.T., Bos, J.L., de Bruin, A., Heck, A.J.R., Guardavaccaro, D. Control of epithelial cell migration and invasion by the IKKβ- and CK1α-mediated degradation of RAPGEF2.
Dev Cell 27(5):574-85, 2013

Karim, R., Tummers, B., Meyers, C., Backendorf, C., Offringa, R., van Ommen, G.B., Melief, C.J.M., M. Boer, J, Guardavaccaro, D., van der Burg, S.H. Human papillomavirus (HPV) upregulates the cellular deubiquitinase UCHL1 to suppress the keratinocyte’s innate immune response.
PLoS Pathogens 9(5), May 2013

Low, T.Y., Magliozzi, R., Guardavaccaro, D., Heck, A.J.R. Unraveling the ubiquitin-regulated signaling networks by mass spectrometry-based proteomics
Proteomics 13(3-4):526-3,7 2013

Kruiswijk, F., Yuniati, L., Magliozzi, R., Low, T.W., Lim, R., Bolder, R., Mohammed, S., Proud, C.G., Heck, A.J.R., Pagano, M., Guardavaccaro, D. Coupled activation-degradation of eEF2K regulates protein synthesis in response to genotoxic stress.
Science Signaling 5(227):ra40, 2012
Comment in: Science Signaling 5(227):pe25, 2012

Ping, Z., Lim, R., Bashir, T., Pagano, M., Guardavaccaro, D. APC/CCdh1 controls the proteasome-mediated degradation of E2F3 during cell cycle exit.
Cell Cycle 11(10):1999-2005, 2012

Tee, J.M., Sartori da Silva, M., Rygiel, A., Muncan, V., Bink, R., van den Brink, G., van Tijn, P., Zivkovic, D., Kodach, L., Guardavaccaro, D., Diks, S., Peppelenbosch, M. Asb11 is a regulator of embryonic and adult regenerative myogenesis.
Stem Cells Dev 21(17):3091-103, 2012

Guardavaccaro, D., Clevers, H. Wnt/β-Catenin and MAPK Signaling: Allies and Enemies in Different Battlefields.
Science Signaling 5(219):pe155, 2012

de Lau, W., Barker, N., Low, T.Y., Koo, B.K., Li, V.S., Teunissen, H., Kujala, P., Haegebarth, A., Peters, P.J., van de Wetering, M., Stange, D.E., van Es, J.E., Guardavaccaro, D., Schasfoort, R.B., Mohri, Y., Nishimori, K., Mohammed, S., Heck, A.J., Clevers, H. Lgr5 homologues associate with Wnt receptors and mediate R-spondin signalling.
Nature 476(7360):293-7, 2011
Comment in: Nature 476(7360), 2011

Sartori da Silva, M.A., Tee, J.M., Paridaen, J., Brouwers, A., Runtuwene, V., Zivkovic, D., Diks, S.H., Guardavaccaro, D., Peppelenbosch, M.P. Essential role for the d-Asb11 cul5 Box domain for proper notch signaling and neural cell fate decisions in vivo.
PLoS One 5(11):e14023, 2010

Dehan, E., Bassermann, F., Guardavaccaro, D., Vasiliver-Shamis, G., Cohen, M.S., Lowes, K.N., Dustin, M., Huang, D.S., Taunton, J., Pagano, M. TrCP- and Rsk1/2-mediated degradation of BimEL inhibits apoptosis.
Mol Cell 33(1):109-16, 2009.

Frescas, D., Guardavaccaro, D., Kuchay, S.M., Kato, H., Poleshko, A., Basrur, V., Elenitoba-Johnson, K.S., Katz, R.A., Pagano, M. KDM2A represses transcription of centromeric satellite repeats and maintains the heterochromatic state.
Cell Cycle 7(22):3539-47, 2008.
Comment in: Cell Cycle 7(22):3479-80, 2008

Bassermann, F., Frescas, D., Guardavaccaro, D., Busino, L., Peschiaroli, A., Pagano, M. The Cdc14B-Cdh1-Plk1 axis in the control of the G2 DNA damage response checkpoint.
Cell 134(2):256-67, 2008.
Comment in: Cell 134(2):210-2, 2008

Zhao, X., Ik-Tsen Heng, J., Guardavaccaro, D., Jiang, R., Pagano, M., Guillemot, F., Iavarone, A., Lasorella, A. The HECT-domain ubiquitin ligase Ureb1 controls neural differentiation and proliferation by destabilizing the N-Myc oncoprotein.
Nat Cell Biol 10(6):643-53, 2008

Michaelson, D., Abidi, W., Guardavaccaro, D., Zhou, M., Ahearn, I., Pagano, M., Philips, M.R. Rac1 accumulates in the nucleus during the G2 phase of the cell cycle and promotes cell division.
J Cell Biol 181(3), 485-496, 2008.

Guardavaccaro, D., Frescas, D., Dorrello, N.V., Peschiaroli, A., Multani, A.S., Cardozo, T., Lasorella, A., Iavarone, A., Chang, S., Hernando, E., Pagano, M. Control of chromosome stability by the βTRCP-REST-MAD2 axis.
Nature 452(7185) 365-70, 2008.
Comment in: Cancer Cell. 13(5):381-3, 2008
Comment in: Nature Reviews Cancer. 8(5):327, 2008



Frescas, D., Guardavaccaro, D., Bassermann, F., Koyama-Nasu, R., Pagano, M. The histone demethylase JHDM1B/FBXL10 is a nucleolar protein that represses transcription of ribosomal RNA genes.
Nature 450(7167) 309-13, 2007.

Amador, V., Ge, S., Santamaria, P.G., Guardavaccaro, D., Pagano, M. APC/CCdc20 controls the ubiquitin-mediated degradation of p21 in prometaphase
Mol Cell 27(3):462-73, 2007.

Fielenbach, N., Guardavaccaro, D., Neubert, K., Chan, T., Li, D., Feng, Q., Hutter, H., Pagano M., Antebi A. DRE-1, an evolutionarily conserved F-box protein that regulates C. elegans developmental age.
Dev Cell 12(3):443-55, 2007.

Dorrello, N.V., Peschiaroli, A., Guardavaccaro, D., Colburn, N.H., Sherman, N.E., Pagano, M. SCFβTrCP- and S6K1-mediated degradation of PDCD4 promotes protein translation and cell growth.
Science 314(5798):467-71, 2006.
Comment in: Science 314(5798):428-9, 2006

Peschiaroli, A., Dorrello, N.V., Guardavaccaro, D., Venere, M., Halazonetis, T., Sherman, N.E., Pagano, M. SCFβTrCP-mediated degradation of Claspin regulates recovery from the DNA replication checkpoint response.
Mol Cell 23(3):319-29, 2006.
Comment in: Curr Biol 16(21):R932-4, 2006

Lasorella, A., Stegmüller, J. Guardavaccaro, D., Liu, G., Carro, M.S., Rothschild, G., de la Torre-Ubieta, L., Pagano, M., Bonni, A., Iavarone, A. Degradation of Id2 by the Anaphase Promoting Complex couples control of cell cycle exit and axonal growth.
Nature 442(7101):471-4, 2006.
Comment in: Nature 442(7101):365-6, 2006

Ji, P., Goldin, L., Ren, H., Sun, D., Guardavaccaro, D., Pagano, M., Zhu, L. Skp2 contains a novel cyclin A binding domain that directly protects cyclin A from inhibition by p27.
J Biol Chem 281(33):24058-69, 2006.

Guardavaccaro, D., Pagano M. Stabilizers and destabilizers controlling cell cycle oscillators.
Mol Cell 22(1):1-4, 2006.

Kudo, Y.*, Guardavaccaro, D.*, Gonzalez Santamaria, P., Koyama-Nasu, R., Latres, E. Bronson, R. Yamasaki, L. Pagano M. Role of F-box protein βTrCP1 in mammary gland development and tumorigenesis.
Mol Cell Biol 24(18):8184-8194, 2004. *Equal contribution.

Guardavaccaro, D., Pagano, M. Oncogenic aberrations of cullin-dependent ubiquitin ligases.
Oncogene 23(11):2037-49, 2004.

Bashir, T., Dorrello, N.V., Amador, V., Guardavaccaro, D., Pagano, M. Control of the SCFSkp2-Cks1 ubiquitin ligase by the APC/CCdh1 ubiquitin ligase.
Nature 428(6979):190-3, 2004.
Comment in: Nature Reviews Molecular Cell Biology 5, 339 2004

Busino, L., Donzelli, M., Chiesa, M., Guardavaccaro, D., Ganoth, D., Dorrello, N.V., Hershko, A., Pagano M., Draetta G. Ubiquitin-mediated degradation of Cdc25A by βTrCP during S phase and in response to DNA damage.
Nature 426(6962):87-9, 2003.

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 βTrCP1 in vivo.
Dev Cell 4: 799–812, 2003.
Comment in: Mol Cell 11(6):1420-1, 2003

Corrente, G., Guardavaccaro, D., Tirone, F. PC3 potentiates NGF-induced differentiation and protects neurons from apoptosis.
Neuroreport 13(4):417-22, 2002.

Guardavaccaro, D., Corrente, G., Covone, F., Micheli, L., D’Agnano, I., Starace, G., Caruso M., Tirone F. Arrest of G(1)-S progression by the p53-inducible gene PC3 is Rb dependent and relies on the inhibition of cyclin D1 transcription.
Mol Cell Biol 20: 1797-815, 2000.

Cenciarelli, C., Chiaur, D. S., Guardavaccaro, D., Parks, W., Vidal, M., Pagano M. Identification of a family of human F-box proteins.
Curr Biol 9: 1177-1179, 1999.

Buanne, P., Incerti, B., Guardavaccaro, D., Avvantaggiato, V., Simeone A., Tirone F. Cloning of the human Interferon-Related Developmental Regulator (IFRD1) gene coding for the PC4 protein, member of a novel family of developmentally regulated genes.
Genomics 51: 233-42, 1998.

Montagnoli, A., Guardavaccaro, D., Starace G., Tirone F. Overexpression of the PC3 immediate early gene is associated to inhibition of cell proliferation.
Cell Growth Differ 7: 1327-1336, 1996.

Guardavaccaro, D., Ciotti, M.T., Schafer, B.W., Montagnoli A., Tirone F. Inhibition of differentiation in myoblasts deprived of the interferon-related protein PC4.
Cell Growth Differ 6: 159-169, 1995.

Guardavaccaro, D., Montagnoli, A., Ciotti, M.T., Lotti, L., Di Lazzaro, C., Torrisi, M.R., Gatti A., Tirone F. Nerve Growth Factor regulates the subcellular localization of the NGF inducible protein PC4 in PC12 cells.
J Neurosci Res 37: 660-674, 1994.