Institute of Protein Biochemistry, CNR.
Via P. Castellino, 111 - 80131 Napoli
2019 IBP Seminar Series
CNR Conference Room
Thursday, February 21st, 2019 at 14.30
Patrizia Lavia, PhD
Institute of Molecular Biology and Pathology - CNR
Department of Biology and Biotechnology "Charles Darwin"
University "La Sapienza" - Rome
"Nuclear transport receptors, SUMOylation and cancer"
Host: Dr. Daniela Corda (phone: (+39) 081 6132536; e-mail: email@example.com)
Mitosis requires the coordinated activity of hundreds of proteins that cyclically cooperate to build-up the mitotic spindle and organise chromosome segregation. These processes are highly regulated in space and time. Errors, if not corrected, can originate genetically unstable cells, a typical cancer hallmark.
Importin beta (or kariopherin beta, Kpn1) and exportin 1/CRM1 are nuclear transport receptors. They operate as vectors for protein cargoes carrying nuclear or cytoplasmic localisation signals during nucleocytoplasmic transport in interphase cells. After nuclear envelope breakdown, they are functionally repurposed to act as regulators of mitosis. Both are overexpressed in many types of cancers that display high levels of genetic instability originating during abnormal mitotic divisions. Understanding the molecular mechanisms and partners through which nuclear transport receptors regulate mitosis is therefore an important challenge that can help understanding the onset of genetic instability and its progression during tumorigenesis.
To gain that understanding, in recent years we have undertaken an "omics" analysis of importin beta-dependent interaction networks in mitotic cells. By integrating proteomic analyses, imaging and cell-based functional assays, we have defined mitotic profiles of importin beta interactors. That has led us to identify several interesting pathways orchestrated by importin beta. The final goal is to identify cancer-specific "vulnerabilities" that can be rationally exploited to devise effective synergic combinations to treat cancers that overexpress importin beta.