nection to p 53 - Dependent Stress Response

nloaded s-of-function mutations of retinoblastoma family (Rb) proteins drive tumorigenesis by overcoming baro cellular proliferation. Consequently, factors modulating Rb function are of great clinical import. Here, ow that miR-335 is differentially expressed in human cancer cells and that it tightly regulates the exon of Rb1 (pRb/p105) by specifically targeting a conserved sequence motif in its 3′ untranslated region. und that by altering Rb1 (pRb/p105) levels, miR-335 activates the p53 tumor suppressor pathway to limit oliferation and neoplastic cell transformation. DNA damage elicited an increase in miR-335 expression 3-dependent manner. miR-335 and p53 cooperated in a positive feedback loop to drive cell cycle arrest. er, these results indicate that miR-335 helps control proliferation by balancing the activities of the Rb Togeth and p53 tumor suppressor pathways. Further, they establish that miR-335 activation plays an important role in the induction of p53-dependent cell cycle arrest after DNA damage. Cancer Res; 70(17); 6925–33. ©2010 AACR.