TRIP12 siRNA – E3 Ubiquitin-Protein Ligase TRIP12 (Rat)

TRIP12: E3 ubiquitin-protein ligase involved in ubiquitin fusion degradation (UFD) pathway and regulation of DNA repair. Part of the ubiquitin fusion degradation (UFD) pathway, a process that mediates ubiquitination of protein at their N-terminus, regardeless of the presence of lysine residues in target proteins. In normal cells, mediates ubiquitination and degradation of isoform p19ARF/ARF of CDKN2A, a lysine-less tumor suppressor required for p53/TP53 activation under oncogenic stress. In cancer cells, however, isoform p19ARF/ARF and TRIP12 are located in different cell compartments, preventing isoform p19ARF/ARF ubiquitination and degradation. Does not mediate ubiquitination of isoform p16-INK4a of CDKN2A. Also catalyzes ubiquitination of NAE1 and SMARCE1, leading to their degradation. Ubiquitination and degradation of target proteins is regulated by interaction with proteins such as MYC, TRADD or SMARCC1, which disrupt the interaction between TRIP12 and target proteins. Acts as a key regulator of DNA damage response by acting as a suppressor of RNF168, an E3 ubiquitin-protein ligase that promotes accumulation of 'Lys-63'-linked histone H2A and H2AX at DNA damage sites, thereby acting as a guard against excessive spreading of ubiquitinated chromatin at damaged chromosomes. Belongs to the UPL family. K-HECT subfamily. 4 isoforms of the human protein are produced by alternative splicing.

Protein type: Nuclear receptor co-regulator; EC 6.3.2.-; Ubiquitin conjugating system; EC 6.3.2.19; Ubiquitin ligase; Ligase

Cellular Component: nucleoplasm; cytoplasm; nucleus

Molecular Function: zinc ion binding; ubiquitin-protein ligase activity; thyroid hormone receptor binding; ligase activity

Biological Process: protein ubiquitination during ubiquitin-dependent protein catabolic process; protein ubiquitination; DNA repair; response to DNA damage stimulus