STUDY OF THE ROLE OF UBIQUITIN PROTEIN LIGASE CRL4CDT2 IN THE CONTROL OF CHROMATIN REMODELING FACTOR

JULIANA ENRIQUÉ STEINBERG; FABIANA ROSSI; FLORENS L; MICHELE PAGANO; MARIO ROSSI

Mar del Plata

Congreso; SAIB - 51 Annual Meeting Argentine Society for Biochemistry and Molecular Biology; 2015

The Ubiquitin-Proteasome System is a major coordinator of cellular physiology through the regulation of protein homeostasis and its substrate specificity is tightly regulated by the family of E3 ubiquitin ligases. CRL4Cdt2 ubiquitin ligase is emerging as a master regulator of cellular proliferation involved in multiple DNA repair processes, which is frequently over-expressed in a variety of human tumors and its expression correlates with tumor grade, metastasis and poor survival. However, despite the broad and potentially important implications for cancer biology, the precise molecular mechanisms by which CRL4Cdt2 exerts its oncogenic activity are still far from being understood. In order to broaden our understanding how deregulation of CRL4Cdt2 might contribute to cancer development, we used an affinity purification and mass spectrometry approach to identify and characterize new CRL4Cdt2 substrates. Among the most abundant putative Cdt2 protein interacting factors identified, we focused our attention on different members of a multi-protein complex implicated in the maintenance of chromatin structure. These proteins play an important role as barriers of cancer stem cell self-renewal and thus the characterization of their functional interaction with CRL4Cdt2 might unveil new potential therapeutic point of intervention in cancer treatment.