NDLI: Ubiquitylation of p53 by the APC/C inhibitor Trim39

Content Provider	PubMed Central
Author	Zhang, Liguo Huang, Nai-jia Chen, Chen Tang, Wanli Kornbluth, Sally
Abstract	Tripartite motif 39 (Trim39) is a RING domain-containing E3 ubiquitin ligase able to inhibit the anaphase-promoting complex (APC/C) directly. Through analysis of Trim39 function in p53-positive and p53-negative cells, we have found, surprisingly, that p53-positive cells lacking Trim39 could not traverse the G1/S transition. This effect did not result from disinhibition of the APC/C. Moreover, although Trim39 loss inhibited etoposide-induced apoptosis in p53-negative cells, apoptosis was enhanced by Trim39 knockdown in p53-positive cells. Furthermore, we show here that the Trim39 can directly bind and ubiquitylate p53 in vitro and in vivo, leading to p53 degradation. Depletion of Trim39 significantly increased p53 protein levels and cell growth retardation in multiple cell lines. We found that the relative importance of Trim39 and the well-characterized p53-directed E3 ligase, murine double minute 2 (MDM2), varied between cell types. In cells that were relatively insensitive to the MDM2 inhibitor, nutlin-3a, apoptosis could be markedly enhanced by siRNA directed against Trim39. As such, Trim39 may serve as a potential therapeutic target in tumors with WT p53 when MDM2 inhibition is insufficient to elevate p53 levels and apoptosis.
Related Links	http://dx.doi.org/10.1073/pnas.1212047110
Ending Page	20936
Page Count	6
Starting Page	20931
File Format	PDF
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	51
Volume Number	109
Language	English
Publisher	National Academy of Sciences
Publisher Date	2012-12-18
Access Restriction	Open
Rights Holder	National Academy of Sciences
Subject Keyword	General Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Ubiquitylation of p53 by the APC/C inhibitor Trim39.

Synergistic Blockade of Mitotic Exit by Two Chemical Inhibitors of the APC/C

Non-proteolytic ubiquitylation counteracts the APC/C-inhibitory function of XErp1

Structural analysis of human Cdc20 supports multisite degron recognition by APC/C

Regulation of ciliary polarity by the APC/C

Mutations in APC, Kirsten-ras, and p53—alternative geneticpathways to colorectal cancer

The Trim39 ubiquitin ligase inhibits APC/CCdh1-mediated degradation of the Bax activator MOAP-1

Domain-specific c-Myc ubiquitylation controls c-Myc transcriptional and apoptotic activity

E3 ubiquitin ligase APC/C-Cdh1 accounts for the Warburg effect by linking glycolysis to cell proliferation

Ubiquitylation of p53 by the APC/C inhibitor Trim39

Similar Documents

Ubiquitylation of p53 by the APC/C inhibitor Trim39.

Synergistic Blockade of Mitotic Exit by Two Chemical Inhibitors of the APC/C

Non-proteolytic ubiquitylation counteracts the APC/C-inhibitory function of XErp1

Structural analysis of human Cdc20 supports multisite degron recognition by APC/C

Regulation of ciliary polarity by the APC/C

Mutations in APC, Kirsten-ras, and p53—alternative geneticpathways to colorectal cancer

The Trim39 ubiquitin ligase inhibits APC/CCdh1-mediated degradation of the Bax activator MOAP-1

Domain-specific c-Myc ubiquitylation controls c-Myc transcriptional and apoptotic activity

E3 ubiquitin ligase APC/C-Cdh1 accounts for the Warburg effect by linking glycolysis to cell proliferation

Ubiquitylation of p53 by the APC/C inhibitor Trim39