The TRC8 ubiquitin ligase is sterol regulated and interacts with lipid and protein biosynthetic pathways.

ABSTRACT: TRC8/RNF139 encodes an endoplasmic reticulum-resident E3 ubiquitin ligase that inhibits growth in a RING- and ubiquitylation-dependent manner. TRC8 also contains a predicted sterol-sensing domain. Here, we report that TRC8 protein levels are sterol responsive and that it binds and stimulates ubiquitylation of the endoplasmic reticulum anchor protein INSIG. Induction of TRC8 destabilized the precursor forms of the transcription factors SREBP-1 and SREBP-2. Loss of SREBP precursors was proteasome dependent, required a functional RING domain, occurred without generating processed nuclear forms, and suppressed SREBP target genes. TRC8 knockdown had opposite effects in sterol-deprived cells. In Drosophila, growth inhibition by DTrc8 was genetically suppressed by loss of specific Mprlp, Padlp N-

SUBMITTER: Lee JP 

PROVIDER: S-EPMC3086825 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature