HSPA5 negatively regulates lysosomal activity through ubiquitination of MUL1 in head and neck cancer.

ABSTRACT: HSPA5/GRP78/BiP plays an important role in cell survival or tumor progression. For these reasons, HSPA5 is an emerging therapeutic target in cancer development. Here we report that HSPA5 contributes to head and neck cancer (HNC) survival via maintenance of lysosomal activity; however, a nonthermal plasma (NTP, considered as a next-generation cancer therapy)-treated solution (NTS) inhibits HNC progression through HSPA5-dependent alteration of lysosomal activity. HSPA5 prevents NTS-induced lysosome inhibition through lysosomal-related proteins or regulation of gene expression. However, NTS-induced MUL1/MULAN/GIDE/MAPL (mitochondrial ubiquitin ligase activator of NFKB 1) leads to downregulation of HSPA5 via K48-linked ubiquitination at the lysine 446 (K446) residue. MUL1 knockdown hinders NTS

SUBMITTER: Kim SY 

PROVIDER: S-EPMC5915028 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature