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

Ramakrishna Suresh, Bharathi Suresh, Eung Ji Lee, Hey Jin Lee, Woong Shick Ahn, Kwang Hyun Baek

Research output: Contribution to journalArticle

30 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)10505-10514
Number of pages10
JournalJournal of Biological Chemistry
Volume286
Issue number12
DOIs
StatePublished - 2011 Mar 25

Fingerprint

Histone Deacetylases
Polyubiquitin
Assays
Cells
Co-Repressor Proteins
Neoplasms
Matrix-Assisted Laser Desorption-Ionization Mass Spectrometry
Cell proliferation
Substrates
Ubiquitin
Immunoprecipitation
Tumors
Cell Survival
Cell Proliferation
Apoptosis
Carcinoma
Enzymes
Growth
Therapeutics

Cite this

Suresh, Ramakrishna ; Suresh, Bharathi ; Lee, Eung Ji ; Lee, Hey Jin ; Ahn, Woong Shick ; Baek, Kwang Hyun. / Lys-63-specific deubiquitination of SDS3 by USP17 regulates HDAC activity. In: Journal of Biological Chemistry. 2011 ; Vol. 286, No. 12. pp. 10505-10514.
@article{a9786a6c89da4a0085470bc963c31a27,
title = "Lys-63-specific deubiquitination of SDS3 by USP17 regulates HDAC activity",
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.",
author = "Ramakrishna Suresh and Bharathi Suresh and Lee, {Eung Ji} and Lee, {Hey Jin} and Ahn, {Woong Shick} and Baek, {Kwang Hyun}",
year = "2011",
month = "3",
day = "25",
doi = "10.1074/jbc.M110.162321",
language = "English",
volume = "286",
pages = "10505--10514",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
number = "12",

}

Lys-63-specific deubiquitination of SDS3 by USP17 regulates HDAC activity. / Suresh, Ramakrishna; Suresh, Bharathi; Lee, Eung Ji; Lee, Hey Jin; Ahn, Woong Shick; Baek, Kwang Hyun.

In: Journal of Biological Chemistry, Vol. 286, No. 12, 25.03.2011, p. 10505-10514.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Lys-63-specific deubiquitination of SDS3 by USP17 regulates HDAC activity

AU - Suresh, Ramakrishna

AU - Suresh, Bharathi

AU - Lee, Eung Ji

AU - Lee, Hey Jin

AU - Ahn, Woong Shick

AU - Baek, Kwang Hyun

PY - 2011/3/25

Y1 - 2011/3/25

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=79953218117&partnerID=8YFLogxK

U2 - 10.1074/jbc.M110.162321

DO - 10.1074/jbc.M110.162321

M3 - Article

C2 - 21239494

AN - SCOPUS:79953218117

VL - 286

SP - 10505

EP - 10514

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 12

ER -