14-3-3Tau regulates ubiquitin-independent proteasomal degradation of p21, a novel mechanism of p21 downregulation in breast cancer.

ABSTRACT: 14-3-3 proteins regulate many cellular functions, including proliferation. However, the detailed mechanisms by which they control the cell cycle remain to be fully elucidated. We report that one of the 14-3-3 isoforms, 14-3-3tau, is required for the G(1)/S transition through its role in ubiquitin-independent proteasomal degradation of p21. 14-3-3tau binds to p21, MDM2, and the C8 subunit of the 20S proteasome in G(1) phase and facilitates proteasomal targeting of p21. This function of 14-3-3tau may be deregulated in cancer. The overexpression of 14-3-3tau is frequently found in primary human breast cancer and correlates with lower levels of p21 and shorter patient survival. Tenascin-C, an extracellular matrix protein involved in tumor initiation and progression and a known 14-3-3tau induce

SUBMITTER: Wang B 

PROVIDER: S-EPMC2832502 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature