Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

TRIM33 is an oncogenic transcriptional coactivator stabilizing AR from Skp2-mediated ubiquitin-proteasomal degradation in prostate cancer

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE174590 | GEO | 2022/05/05

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

TRIM33 is an oncogenic transcriptional coactivator stabilizing AR from Skp2-mediated ubiquitin-proteasomal degradation in prostate cancer [RNA-Seq]

Project description:Using a proteomics approach, we identified the Tripartite Motif Containing 33 (TRIM33) as a novel transcriptional coactivator of AR. We demonstrate TRIM33 facilitates the AR chromatin binding to directly regulate a transcription program that promotes PCa progression by protecting AR from Skp2-mediated ubiquitination and proteasomal degradation. We also show TRIM33 is essential for PCa tumor growth by avoiding cell cycle arrest and apoptosis, and TRIM33 knockdown sensitizes PCa cells to AR antagonists. In clinical analyses, we find TRIM33 is upregulated in multiple PCa patient cohorts. Finally, we uncover an AR-TRIM33 coactivated gene signature that is highly expressed in PCa tumors and predicts disease recurrence. Overall, our results reveal TRIM33 is an oncogenic AR coactivator in PCa and a potential therapeutic target for PCa treatment.

2022-05-05 | GSE174589 | GEO

TRIM33 is an oncogenic transcriptional coactivator stabilizing AR from Skp2-mediated ubiquitin-proteasomal degradation in prostate cancer [ChIP-seq]

2022-05-05 | GSE174109 | GEO

TRIM33 is an oncogenic transcriptional coactivator stabilizing AR from Skp2-mediated ubiquitin-proteasomal degradation in prostate cancer

Project description:TRIM33 is an oncogenic transcriptional coactivator stabilizing AR from Skp2-mediated ubiquitin-proteasomal degradation in prostate cancer

| PRJNA730585 | ENA

TRIM33 is an oncogenic transcriptional coactivator stabilizing AR from Skp2-mediated ubiquitin-proteasomal degradation in prostate cancer [ChIP-seq]

Project description:TRIM33 is an oncogenic transcriptional coactivator stabilizing AR from Skp2-mediated ubiquitin-proteasomal degradation in prostate cancer [ChIP-seq]

| PRJNA728353 | ENA

TRIM33 is an oncogenic transcriptional coactivator stabilizing AR from Skp2-mediated ubiquitin-proteasomal degradation in prostate cancer [RNA-Seq]

Project description:TRIM33 is an oncogenic transcriptional coactivator stabilizing AR from Skp2-mediated ubiquitin-proteasomal degradation in prostate cancer [RNA-Seq]

| PRJNA730586 | ENA

TRIM33 drives prostate tumor growth by stabilizing androgen receptor from Skp2-mediated degradation

Project description:Androgen receptor (AR) is a master transcription factor that drives prostate cancer (PCa) development and progression. Alterations in the expression or activity of AR coregulators significantly impact the outcome of the disease. Using a proteomics approach, we identified the Tripartite Motif Containing 33 (TRIM33) as a novel transcriptional coactivator of AR. We demonstrate that TRIM33 facilitates AR chromatin binding to directly regulate a transcription program that promotes PCa progression. TRIM33 further stabilizes AR by protecting it from Skp2-mediated ubiquitination and proteasomal degradation. We also show that TRIM33 is essential for PCa tumor growth by avoiding cell cycle arrest and apoptosis, and TRIM33 knockdown sensitizes PCa cells to AR antagonists. In clinical analyses, we find TRIM33 upregulated in multiple PCa patient cohorts. Finally, we uncover an AR-TRIM33 coactivated gene signature highly expressed in PCa tumors and predicts disease recurrence. Overall, our results reveal that TRIM33 is an oncogenic AR coactivator in PCa and a potential therapeutic target for PCa treatment.

| S-SCDT-EMBOR-2021-53468-T | biostudies-other

Cellular TRIM33 restrains HIV-1 infection by targeting viral integrase for proteasomal degradation.

Project description:Productive HIV-1 replication requires viral integrase (IN), which catalyzes integration of the viral genome into the host cell DNA. IN, however, is short lived and is rapidly degraded by the host ubiquitin-proteasome system. To identify the cellular factors responsible for HIV-1 IN degradation, we performed a targeted RNAi screen using a library of siRNAs against all components of the ubiquitin-conjugation machinery using high-content microscopy. Here we report that the E3 RING ligase TRIM33 is a major determinant of HIV-1 IN stability. CD4-positive cells with TRIM33 knock down show increased HIV-1 replication and proviral DNA formation, while those overexpressing the factor display opposite effects. Knock down of TRIM33 reverts the phenotype of an HIV-1 molecular clone carrying substitution of IN serine 57 to alanine, a mutation known to impair viral DNA integration. Thus, TRIM33 acts as a cellular factor restricting HIV-1 infection by preventing provirus formation.

| S-EPMC6389893 | biostudies-literature

Skp2 regulates androgen receptor through ubiquitin-mediated degradation independent of Akt/mTOR pathways in prostate cancer.

Project description:The intervention of advanced prostate cancer (PCa) in patients has been commonly depending on androgen deprivation therapy. Despite of tremendous research efforts, however, molecular mechanisms on AR regulation remain poorly understood, particularly for castration resistant prostate cancer (CRPC). Targeting AR and associated factors is considered an effective strategy in PCa treatment.Human prostate cancer cells were used in this study. Manipulations of Skp2 expression were achieved by Skp2 shRNA/siRNA or overexpression of plasmids. Dual luciferase reporter assay was applied for AR activity assessment. Western blot, ubiquitination assay, immunoprecipitation, and immunofluorescence were applied to detect the proteins.Our results demonstrated that Skp2 directly involves the regulation of AR expression through ubiquitination-mediated degradation. Skp2 interacted with AR protein in PCa cells, and enforced expression of Skp2 resulted in a decreased level and activity of AR. By contrast, Skp2 knockdown increased the protein accumulation and activity of AR. Importantly, changes of AR contributed by Skp2 led to subsequent alterations of PSA level in PCa cells. AR ubiquitination was significantly increased upon Skp2 overexpression but greatly reduced upon Skp2 knockdown. AR mutant at K847R abrogated Skp2-mediated ubiquitination of AR. NVP-BEZ235, a dual PI3K/mTOR inhibitor, remarkably inhibited Skp2 level with a striking elevation of AR.The results indicate that Skp2 is an E3 ligase for proteasome-dependent AR degradation, and K847 on AR is the recognition site for Skp2-mediated ubiquitination. Our findings reveal an essential role of Skp2 in AR signaling.

| S-EPMC4062570 | biostudies-literature

Ubiquitin-like and ubiquitin-associated domain proteins: significance in proteasomal degradation.

Project description:The ubiquitin-proteasome pathway of protein degradation is one of the major mechanisms that are involved in the maintenance of the proper levels of cellular proteins. The regulation of proteasomal degradation thus ensures proper cell functions. The family of proteins containing ubiquitin-like (UbL) and ubiquitin-associated (UBA) domains has been implicated in proteasomal degradation. UbL-UBA domain containing proteins associate with substrates destined for degradation as well as with subunits of the proteasome, thus regulating the proper turnover of proteins.

| S-EPMC2725189 | biostudies-literature

Targeting AR Variant-Coactivator Interactions to Exploit Prostate Cancer Vulnerabilities.

Project description:Castration-resistant prostate cancer (CRPC) progresses rapidly and is incurable. Constitutively active androgen receptor splice variants (AR-Vs) represent a well-established mechanism of therapeutic resistance and disease progression. These variants lack the AR ligand-binding domain and, as such, are not inhibited by androgen deprivation therapy (ADT), which is the standard systemic approach for advanced prostate cancer. Signaling by AR-Vs, including the clinically relevant AR-V7, is augmented by Vav3, an established AR coactivator in CRPC. Using mutational and biochemical studies, we demonstrated that the Vav3 Diffuse B-cell lymphoma homology (DH) domain interacted with the N-terminal region of AR-V7 (and full length AR). Expression of the Vav3 DH domain disrupted Vav3 interaction with and enhancement of AR-V7 activity. The Vav3 DH domain also disrupted AR-V7 interaction with other AR coactivators: Src1 and Vav2, which are overexpressed in PC. This Vav3 domain was used in proof-of-concept studies to evaluate the effects of disrupting the interaction between AR-V7 and its coactivators on CRPC cells. This disruption decreased CRPC cell proliferation and anchorage-independent growth, caused increased apoptosis, decreased migration, and resulted in the acquisition of morphological changes associated with a less aggressive phenotype. While disrupting the interaction between FL-AR and its coactivators decreased N-C terminal interaction, disrupting the interaction of AR-V7 with its coactivators decreased AR-V7 nuclear levels.Implications: This study demonstrates the potential therapeutic utility of inhibiting constitutively active AR-V signaling by disrupting coactivator binding. Such an approach is significant, as AR-Vs are emerging as important drivers of CRPC that are particularly recalcitrant to current therapies. Mol Cancer Res; 15(11); 1469-80. ©2017 AACR.

| S-EPMC5770277 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data