Notch3 functions as a tumor suppressor by controlling cellular senescence.

ABSTRACT: Notch signaling regulates a broad spectrum of cell fate decisions and differentiation. Both oncogenic and tumor suppressor functions have been shown for Notch signaling. However, little is known about the underlying mechanisms of its tumor suppressor function. Here, we report that expression of Notch3, a member of Notch family transmembrane receptors, was elevated in human cells during senescence activated by various senescence-inducing stimuli. This upregulation of Notch3 was required for the induction of p21 expression in senescent cells. Downregulation of Notch3 led to a delayed onset of senescence and extended replicative lifespan, whereas adventitious expression of Notch3 was sufficient to activate senescence and p21 expression. The ability of Notch3 to induce senescence and p21 expre

SUBMITTER: Cui H 

PROVIDER: S-EPMC3674178 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature