Genetic interrogation of replicative senescence uncovers a dual role for USP28 in coordinating the p53 and GATA4 branches of the senescence program

• DOI: 10.1101/gad.304857.117
• Publication Date: 2017-10-31T15:41:45Z
• Authors: Anna E. Mazzucco; Agata Smogorzewska; Chanhee Kang; Ji Luo; Michael R. Schlabach; Qikai Xu; Rupesh Patel; Stephen J. Elledge
• Keywords: Senescence

Senescence is a terminal differentiation program that halts the growth of damaged cells and must be circumvented for cancer to arise. Here we describe panel genetic screens identify genes required replicative senescence. We uncover role in senescence potent tumor suppressor ATM substrate USP28. USP28 controls activation both TP53 branch GATA4/NFkB senescence-associated secretory phenotype (SASP). These results suggest ubiquitination imply common node downstream from links GATA4 branches response.