IndraLab
Statements
sparser
"In the current study we hypothesize that electrophilic OB compounds, such as 4,4'-diamino-2,2'-stilbenedisulfonic acid(DAST), fluorescent brightener 28 (FB-28) and FB-71, can interact with the catalytic triads (CYS, HIS, and ASP) of UCHL5 and USP14 and inhibit their enzymatic activities, leading to cell growth suppression."
sparser
"In addition to Rpn11 ubiquitin hydrolase, which is also a metalloprotease, there are several other de-ubiquitinating proteins, USP14 (ubiquitin-specific protease 14) and UCH37 (ubiquitin C-terminal hydrolase 37), which loosely associate with the 19S regulatory particle yet modulate the trimming of ubiquitins [ xref ]."
sparser
"Rpn11 is a stoichiometric subunit of the lid subcomplex of the 19S regulatory particle whereas USP14 and UCHL5 reversibly associate with the 19S, indicative of attractive and versatile roles for these molecules. xref , xref , xref , xref As a member of the ubiquitin-specific processing protease family, USP14 has been reported to be highly expressed in several kinds of carcinoma, including multiple myeloma, xref ovarian carcinoma xref and colorectal cancer. xref In this study, we have identified that USP14 promotes the cell cycle in prostate carcinoma cells by deubiquitination and stabilization of AR."
sparser
"There are ~98 DUBs encoded by the human genome, which are distributed into six families based on sequence and structural similarities. xref The 19 S regulatory particle of the proteasome harbors three DUBs, each exhibiting notable differences in homology. xref Of the three, USP14 and UCHL5 reversibly associate with the proteasome, whereas the third, RPN11/POH1, is an intrinsic component of the lid subcomplex of the 19 S cap. xref The role of USP14 and UCHL5 in maintaining cancer cell viability and providing growth advantage is increasingly being recognized in a variety of cancers, including hematologic malignancies. xref Although the precise molecular contributions made by these two DUBs towards tumor cell survival continue to be studied, xref , xref , xref , xref , xref , xref efforts to target their dysregulated (and often increased) activity are underway, notably in MM and WM. xref , xref Herein, we extend our initial observations that USP14 and UCHL5 are highly expressed in drug-resistant WM tumor cells including those from WM patients as compared with PBMCs or resident bone marrow cells from healthy donors."
sparser
"The 19S proteasome subunit Rpn11 has deubiquitinase activity that recycles polyubiquitin by removing them en bloc from protein substrates that are committed for degradation. xref Additional deubiquitinases USP14 and UCH37 reversibly interact with the proteasome and can trim ubiquitin chains independent of substrate commitment to degradation. xref , xref , xref "
sparser
"This conclusion is compellingly supported by multiple lines of evidence presented here: (i) our molecular docking analyses predicted that the catalysis of the proteasomal DUBs (USP14 and UCHL5) could be inactive in the presence of bilirubin because bilirubin anion is predicted to strongly bind to the catalytic cores of the two DUBs through both steric effect and forming hydrogen bonds ( xref ); (ii) our DUB active site-directed labeling assays confirmed that bilirubin binds to the active sites of both USP14 and UCHL5 associated with 26S proteasomes ( xref ); (iii) the in vitro DUB activity of purified 26S proteasomes ( xref ), but not that of whole-cell lysates ( xref ), was effectively inhibited by incubation with bilirubin at a dose as low as 3.0 μ M; and (iv) our polyubiquitin chain disassembly assays showed that bilirubin effectively prevented the 26S proteasome from disassembling K48-linked tetraubiquitin chains in vitro ( xref )."
sparser
"We found that the remaining active forms of both UCHL5 and USP14
(i.e., those can be covalently bound by HA-UbVS) were clearly reduced in the 26S
proteasomes pre-treated with Aur at 2 μM and became completely undetectable in
those pre-treated with 40 μM Aur (Fig. xref ), indicating that Aur inhibits both UCHL5 and USP14."
sparser
"Taken together, our results suggest that ITCs could bind to the active sites of USP14 and UCHL5, causing inhibition and inhibition of these DUB activities by ITCs also lead to increased levels of expression of USP14 and UCHL5 proteins, representing activation of a feedback loop (see DISCUSSION)."