IndraLab

Statements


| 16

reach
"Co-depletion of POH1 and RAP80, BRCC36 or ABRAXAS allows establishment of the 53BP1 and ubiquitin chain-devoid core."

reach
"Although Poh1 is best characterized for its essential role in 26S proteasome dependent proteolysis, several lines of evidence indicate that Poh1 activates aggresome clearance mainly by producing free K63 ubiquitin chains."

reach
"POH1 is recruited to the IRIF core in a BRCA1 dependent manner, and promotes the clearance of RAP80, the ubiquitin chain and 53BP1 from the IRIF core in G2 phase cells in the late stages of DDR [XREF_BIBR]."

reach
"Depletion of POH1, a DUB and proteasome subunit, prevents removal of ubiquitin from the core of DSB foci, whereas depletion of both POH1 and RAP80 enables ubiquitin to be removed, consistent with the model that RAP80 preserves polyubiquitin modifications on chromatin [XREF_BIBR]."

reach
"Although it may seem a bit contradictory, we demonstrate that knockdown of POH1 (a deubiquitining enzyme) could diminish the ubiquitin modification of p53 and Bim, and we speculated there were some reasons."

reach
"Rpn11 contributes isopeptidase activity to recycle ubiquitin moieties from the protein substrates."

reach
"If Poh1 promotes aggresome processing by producing unanchored ubiquitin chains, it would be expected that introduction of exogenous free ubiquitin chains should restore aggresome clearance in Poh1 KD cells."

reach
"We present evidence that free ubiquitin chains produced by Poh1 bind and activate the deacetylase, HDAC6, which in turn stimulates actinomyosin- and autophagy dependent aggresome processing."

reach
"Poh1 activates aggresome clearance by producing unanchored K63 ubiquitin chains."

reach
"In principle, free ubiquitin chains can also be produced by Poh1 (RPN11), a JAMM and MPN + -domain containing deubiquitinating enzyme that cleaves off ubiquitin chains en bloc from substrates targeted to the proteasome."

reach
"Finally, K63 linked chains might in some instances promote proteasomal degradation, as suggested by another recent study in The EMBO Journal, and Poh1 could allow recycling of ubiquitin."

reach
"All together, these data revealed a previously undescribed mechanism by which RNF5 and POH1 mediate the ubiquitin modification of SARS-CoV-2 M for virion trafficking and release.As noted by previous studies, unlike with most enveloped viruses, in which M is necessary and sufficient to mediate VLP release, the E/M proteins of murine hepatitis virus (MHV) or the M/E/N proteins of SARS-CoV are necessary for efficient assembly, trafficking, and VLP release (7–9)."

reach
"These findings support the idea that HDAC6 binds K63-linkage containing free ubiquitin chains produced by Poh1 during aggresome clearance."

reach
"POH1 (PSMD14, RPN11) is located close to the entrance to the 20S core, and promotes substrate degradation by cleaving entire Ub chains from substrates, allowing the protein to enter the pore for degradation."

reach
"These results support the conclusion that Poh1 promotes aggresome clearance primarily by producing specific unanchored ubiquitin chains."

reach
"Furthermore, POH1 and Rpn11, a proteasome subunit with deubiquitylation activity, stimulates the formation of IBs by generating free ubiquitin chains in proximity of the aggregated proteins and results in the recruitment of HDAC6, which orchestrates ubiquitin dependent transport of proteins to the aggresome."