A detailed understanding of the nnolecular and cellular events influencing the three key dimensions of cellular life (growth/proliferation, survival, and differentiation) remains a central question in cancer biology. Further understanding of the influence of the ubiquitin system on the transformation process will help to identify novel targets for cancer therapy. The first years of work under CA76584 (started in 1998) set the bases for elucidating the role played by F-box proteins in human oncogenesis, which was accomplished during the second funding cycle. In its third cycle, CA76584 is currently devoted to elucidating the integration of the ubiquitin system in the signaling networks of the cell, and its corruption in cancer. In particular, our research program involves the study of the human family of SCF and SCF-like ubiquitin ligases to gain an understanding of the molecular mechanisms through which they control basic cellular processes, such as cell growth, cell division, and cell survival. To this end, we are using a comprehensive and interdisciplinary approach that includes biochemical and biological methods, as well as somatic cell and mouse genetics. These tools, together with our expertise in the ubiquitin system, will ensure that our laboratory will continue to contribute to the understanding of cell functions during the coming years. As the mechanisms of the ubiquitin-mediated proteolysis of cell cycle regulators are unraveled, this team is committed to the integration of its basic research results with an understanding of malignant transformation.
The knowledge gained from our studies is crucial to understanding the molecular mechanisms of malignant transformation and will facilitate translational research aimed at developing strategies for therapeutic intervention. Indeed, therapeutics that non-specifically target the pathways studied by my laboratory (e.g., proteasome inhibitors) are already a reality, and we hope that our studies will lead to more potent, specific therapeutics.
|Pae, Juhee; Cinalli, Ryan M; Marzio, Antonio et al. (2017) GCL and CUL3 Control the Switch between Cell Lineages by Mediating Localized Degradation of an RTK. Dev Cell 42:130-142.e7|
|Fehrenbacher, Nicole; Tojal da Silva, Israel; Ramirez, Craig et al. (2017) The G protein-coupled receptor GPR31 promotes membrane association of KRAS. J Cell Biol 216:2329-2338|
|Donato, Valerio; Bonora, Massimo; Simoneschi, Daniele et al. (2017) The TDH-GCN5L1-Fbxo15-KBP axis limits mitochondrial biogenesis in mouse embryonic stem cells. Nat Cell Biol 19:341-351|
|Dankert, John F; Rona, Gergely; Clijsters, Linda et al. (2016) Cyclin F-Mediated Degradation of SLBP Limits H2A.X Accumulation and Apoptosis upon Genotoxic Stress in G2. Mol Cell 64:507-519|
|Pagan, Julia K; Marzio, Antonio; Jones, Mathew J K et al. (2015) Degradation of Cep68 and PCNT cleavage mediate Cep215 removal from the PCM to allow centriole separation, disengagement and licensing. Nat Cell Biol 17:31-43|
|Duan, Shanshan; Pagano, Michele (2015) SPOP Mutations or ERG Rearrangements Result in Enhanced Levels of ERG to Promote Cell Invasion in Prostate Cancer. Mol Cell 59:883-4|
|Skaar, Jeffrey R; Ferris, Andrea L; Wu, Xiaolin et al. (2015) The Integrator complex controls the termination of transcription at diverse classes of gene targets. Cell Res 25:288-305|
|Young, Lauren M; Marzio, Antonio; Perez-Duran, Pablo et al. (2015) TIMELESS Forms a Complex with PARP1 Distinct from Its Complex with TIPIN and Plays a Role in the DNA Damage Response. Cell Rep 13:451-459|
|Chen, X; Sahasrabuddhe, A A; Szankasi, P et al. (2014) Fbxo45-mediated degradation of the tumor-suppressor Par-4 regulates cancer cell survival. Cell Death Differ 21:1535-45|
|Choi, Byeong Hyeok; Pagano, Michele; Dai, Wei (2014) Plk1 protein phosphorylates phosphatase and tensin homolog (PTEN) and regulates its mitotic activity during the cell cycle. J Biol Chem 289:14066-74|
Showing the most recent 10 out of 62 publications