Oncogene-induced senescence (OIS) is a protective mechanism through which normal cells defend themselves against transformation. Oncogenic stress (induced by mutation or proto-oncogene overex-pression) activates this tumor-suppres-sive pathway, wherein cells enter a stage of irreversible cell-cycle arrest, thereby restricting uncontrolled cellular proliferation and malignant growth. OIS has been described both in vitro in primary cells, as well as in vivo in pre-malignant lesions, for multiple oncogenes and in various cellular contexts.We recently reported a unique form of OIS activated by overexpression of the oncogenic splicing factor SRSF1. SRSF1 encodes a multi-functional protein with regulatory roles in many aspects of RNA biogenesis and function, including constitutive and alternative splicing, mRNA export and translation. Aberrant SRSF1 activity is deleterious for the cell: SRSF1 depletion triggers genomic instability, cell-cycle arrest and apoptosis, whereas its overexpression leads to oncogenic transformation.
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