Taspase1 functions as a non-oncogene addiction protease that coordinates cancer cell proliferation and apoptosis.

ABSTRACT: Taspase1, the mixed lineage leukemia and TFIIAalpha-beta cleaving protease, enables cell proliferation and permits oncogenic initiation. Here, we show its critical role in cancer maintenance and thus offer a new anticancer target. Taspase1 is overexpressed in primary human cancers, and deficiency of Taspase1 in cancer cells not only disrupts proliferation but also enhances apoptosis. Mechanistically, loss of Taspase1 induces the levels of CDK inhibitors (CDKI: p16, p21, and p27) and reduces the level of antiapoptotic MCL-1. Therapeutically, deficiency of Taspase1 synergizes with chemotherapeutic agents and ABT-737, an inhibitor of BCL-2/BCL-X(L), to kill cancer cells. Taspase1 alone or in conjunction with MYC, RAS, or E1A fails to transform NIH/3T3 cells or primary mouse embryonic fibrobla

SUBMITTER: Chen DY 

PROVIDER: S-EPMC2909739 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature