Inhibition of PHLPP2/cyclin D1 protein translation contributes to the tumor suppressive effect of NFκB2 (p100).

ABSTRACT: Although the precursor protein of NFκB2 (p100) is thought to act as a tumor suppressor in mammalian cells, the molecular mechanism of its anti-tumor activity is far from clear. Here, we are, for the first time, to report that p100 protein expression was dramatically decreased in bladder cancers of N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN)-treated mice and human patients. Knockdown of p100 in cultured human bladder cancer cells promoted anchorage-independent growth accompanied with elevating abundance of cell-cycle-related proteins and accelerated cell-cycle progression. Above effects could be completely reversed by ectopically expression of p100, but not p52. Mechanistically, p100 inhibited Cyclin D1 protein translation by activating the transcription of LARP7 and its hosted miR-302d, w

SUBMITTER: Xu J 

PROVIDER: S-EPMC5085141 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature