303 0

Lys-63-specific deubiquitination of SDS3 by USP17 regulates HDAC activity

Title
Lys-63-specific deubiquitination of SDS3 by USP17 regulates HDAC activity
Author
Ramakrishna Suresh
Keywords
NF-KAPPA-B; UBIQUITIN-PROTEASOME PATHWAY; HISTONE DEACETYLASES; POLYUBIQUITIN CHAINS; MULTIUBIQUITIN CHAIN; INTEGRAL COMPONENT; PROTEIN; ACTIVATION; ENZYMES; CANCER
Issue Date
2011-03
Publisher
Amer SOC Biochemistry Molecular Biology INC
Citation
Journal of Biological Chemistry, 2011, 286(12), P.10505-10514
Abstract
SDS3 is a key component of the histone deacetylase (HDAC)-dependent Sin3A co-repressor complex, serving to maintain its HDAC activity. Here, we report both exogenous and endogenous functional interaction between deubiquitinating enzyme USP17 and human SDS3 by MALDI-TOF-MS, co-immunoprecipitation assay, and GST pull-down assay. In this study, we demonstrated that SDS3 readily undergoes endogenous polyubiquitination, which is associated specifically with Lys-63-branched polyubiquitin chains and not with Lys-48-branched polyubiquitin chains. Further, we also demonstrated that USP17 specifically deubiquitinates Lys-63-linked ubiquitin chains from SDS3 and regulates its biological functions. The deubiquitinating activity of USP17 on SDS3 negatively regulates SDS3-associated HDAC activity. The constitutive expression of USP17 and its substrate SDS3 was involved in the inhibition of anchorage-independent tumor growth and blocks cell proliferation, leading to apoptosis in cervical carcinoma cells. Furthermore, we showed that USP17 and SDS3 mutually interact with each other to regulate cancer cell viability. These data support the possibility that SDS3, being a substrate of USP17, may play an important role in developing a novel therapeutic means to inhibit specific HDAC activities in cancer.
URI
http://www.jbc.org/content/286/12/10505
ISSN
0021-9258; 1083-351X
DOI
10.1074/jbc.M110.162321
Appears in Collections:
GRADUATE SCHOOL OF BIOMEDICAL SCIENCE AND ENGINEERING[S](의생명공학전문대학원) > ETC
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE