Deubiquitinating enzyme USP22 positively regulates c-Myc stability and tumorigenic activity in mammalian and breast cancer cells

Dongyeon Kim; Ahyoung Hong; Hye In Park; Woo Hyun Shin; Lang Yoo; Seo Jeong Jeon; Kwang Chul Chung

doi:10.1002/jcp.25841

Deubiquitinating enzyme USP22 positively regulates c-Myc stability and tumorigenic activity in mammalian and breast cancer cells

Dongyeon Kim, Ahyoung Hong, Hye In Park, Woo Hyun Shin, Lang Yoo, Seo Jeong Jeon, Kwang Chul Chung

Research output: Contribution to journal › Article › peer-review

90 Citations (Scopus)

Abstract

The proto-oncogene c-Myc has a pivotal function in growth control, differentiation, and apoptosis and is frequently affected in human cancer, including breast cancer. Ubiquitin-specific protease 22 (USP22), a member of the USP family of deubiquitinating enzymes (DUBs), mediates deubiquitination of target proteins, including histone H2B and H2A, telomeric repeat binding factor 1, and cyclin B1. USP22 is also a component of the mammalian SAGA transcriptional co-activating complex. In this study, we explored the functional role of USP22 in modulating c-Myc stability and its physiological relevance in breast cancer progression. We found that USP22 promotes deubiquitination of c-Myc in several breast cancer cell lines, resulting in increased levels of c-Myc. Consistent with this, USP22 knockdown reduces c-Myc levels. Furthermore, overexpression of USP22 stimulates breast cancer cell growth and colony formation, and increases c-Myc tumorigenic activity. In conclusion, the present study reveals that USP22 in breast cancer cell lines increases c-Myc stability through c-Myc deubiquitination, which is closely correlated with breast cancer progression.

Original language	English
Pages (from-to)	3664-3676
Number of pages	13
Journal	Journal of Cellular Physiology
Volume	232
Issue number	12
DOIs	https://doi.org/10.1002/jcp.25841
Publication status	Published - 2017 Dec

Bibliographical note

Funding Information:
The authors thank B.S. Atanassov, K.H. Baek, D. A. Sinclair, H.D. Youn, I.K. Chung, B.E. Clurman, and H.S. Park for providing plasmids and J. Choi, C. Lee, and N.H. Cho for providing human breast cancer cell lines. The article was supported by grants from National Research Foundation of Korea (NRF), grant number: 2014M3C7A1064545 and 2015R1A2A2A01003080 to K.C.C.; Korea Health Industry Development Institute (KHIDI), grant number: HI14C0093 to K.C.C.; Yonsei University Future-leading Research Initiative of 2015, grant number: 2015-22-0055 to K.C.C. The authors declare that they have no competing interests.

Publisher Copyright:
© 2017 Wiley Periodicals, Inc.

All Science Journal Classification (ASJC) codes

Physiology
Clinical Biochemistry
Cell Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1002/jcp.25841

Cite this

@article{2a64be0cf87a46e9bb1c951e4453bde4,

title = "Deubiquitinating enzyme USP22 positively regulates c-Myc stability and tumorigenic activity in mammalian and breast cancer cells",

abstract = "The proto-oncogene c-Myc has a pivotal function in growth control, differentiation, and apoptosis and is frequently affected in human cancer, including breast cancer. Ubiquitin-specific protease 22 (USP22), a member of the USP family of deubiquitinating enzymes (DUBs), mediates deubiquitination of target proteins, including histone H2B and H2A, telomeric repeat binding factor 1, and cyclin B1. USP22 is also a component of the mammalian SAGA transcriptional co-activating complex. In this study, we explored the functional role of USP22 in modulating c-Myc stability and its physiological relevance in breast cancer progression. We found that USP22 promotes deubiquitination of c-Myc in several breast cancer cell lines, resulting in increased levels of c-Myc. Consistent with this, USP22 knockdown reduces c-Myc levels. Furthermore, overexpression of USP22 stimulates breast cancer cell growth and colony formation, and increases c-Myc tumorigenic activity. In conclusion, the present study reveals that USP22 in breast cancer cell lines increases c-Myc stability through c-Myc deubiquitination, which is closely correlated with breast cancer progression.",

author = "Dongyeon Kim and Ahyoung Hong and Park, {Hye In} and Shin, {Woo Hyun} and Lang Yoo and Jeon, {Seo Jeong} and Chung, {Kwang Chul}",

note = "Funding Information: The authors thank B.S. Atanassov, K.H. Baek, D. A. Sinclair, H.D. Youn, I.K. Chung, B.E. Clurman, and H.S. Park for providing plasmids and J. Choi, C. Lee, and N.H. Cho for providing human breast cancer cell lines. The article was supported by grants from National Research Foundation of Korea (NRF), grant number: 2014M3C7A1064545 and 2015R1A2A2A01003080 to K.C.C.; Korea Health Industry Development Institute (KHIDI), grant number: HI14C0093 to K.C.C.; Yonsei University Future-leading Research Initiative of 2015, grant number: 2015-22-0055 to K.C.C. The authors declare that they have no competing interests. Publisher Copyright: {\textcopyright} 2017 Wiley Periodicals, Inc.",

year = "2017",

month = dec,

doi = "10.1002/jcp.25841",

language = "English",

volume = "232",

pages = "3664--3676",

journal = "Journal of Cellular Physiology",

issn = "0021-9541",

publisher = "Wiley-Liss Inc.",

number = "12",

}

TY - JOUR

T1 - Deubiquitinating enzyme USP22 positively regulates c-Myc stability and tumorigenic activity in mammalian and breast cancer cells

AU - Kim, Dongyeon

AU - Hong, Ahyoung

AU - Park, Hye In

AU - Shin, Woo Hyun

AU - Yoo, Lang

AU - Jeon, Seo Jeong

AU - Chung, Kwang Chul

N1 - Funding Information: The authors thank B.S. Atanassov, K.H. Baek, D. A. Sinclair, H.D. Youn, I.K. Chung, B.E. Clurman, and H.S. Park for providing plasmids and J. Choi, C. Lee, and N.H. Cho for providing human breast cancer cell lines. The article was supported by grants from National Research Foundation of Korea (NRF), grant number: 2014M3C7A1064545 and 2015R1A2A2A01003080 to K.C.C.; Korea Health Industry Development Institute (KHIDI), grant number: HI14C0093 to K.C.C.; Yonsei University Future-leading Research Initiative of 2015, grant number: 2015-22-0055 to K.C.C. The authors declare that they have no competing interests. Publisher Copyright: © 2017 Wiley Periodicals, Inc.

PY - 2017/12

Y1 - 2017/12

N2 - The proto-oncogene c-Myc has a pivotal function in growth control, differentiation, and apoptosis and is frequently affected in human cancer, including breast cancer. Ubiquitin-specific protease 22 (USP22), a member of the USP family of deubiquitinating enzymes (DUBs), mediates deubiquitination of target proteins, including histone H2B and H2A, telomeric repeat binding factor 1, and cyclin B1. USP22 is also a component of the mammalian SAGA transcriptional co-activating complex. In this study, we explored the functional role of USP22 in modulating c-Myc stability and its physiological relevance in breast cancer progression. We found that USP22 promotes deubiquitination of c-Myc in several breast cancer cell lines, resulting in increased levels of c-Myc. Consistent with this, USP22 knockdown reduces c-Myc levels. Furthermore, overexpression of USP22 stimulates breast cancer cell growth and colony formation, and increases c-Myc tumorigenic activity. In conclusion, the present study reveals that USP22 in breast cancer cell lines increases c-Myc stability through c-Myc deubiquitination, which is closely correlated with breast cancer progression.

AB - The proto-oncogene c-Myc has a pivotal function in growth control, differentiation, and apoptosis and is frequently affected in human cancer, including breast cancer. Ubiquitin-specific protease 22 (USP22), a member of the USP family of deubiquitinating enzymes (DUBs), mediates deubiquitination of target proteins, including histone H2B and H2A, telomeric repeat binding factor 1, and cyclin B1. USP22 is also a component of the mammalian SAGA transcriptional co-activating complex. In this study, we explored the functional role of USP22 in modulating c-Myc stability and its physiological relevance in breast cancer progression. We found that USP22 promotes deubiquitination of c-Myc in several breast cancer cell lines, resulting in increased levels of c-Myc. Consistent with this, USP22 knockdown reduces c-Myc levels. Furthermore, overexpression of USP22 stimulates breast cancer cell growth and colony formation, and increases c-Myc tumorigenic activity. In conclusion, the present study reveals that USP22 in breast cancer cell lines increases c-Myc stability through c-Myc deubiquitination, which is closely correlated with breast cancer progression.

UR - http://www.scopus.com/inward/record.url?scp=85018305805&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85018305805&partnerID=8YFLogxK

U2 - 10.1002/jcp.25841

DO - 10.1002/jcp.25841

M3 - Article

C2 - 28160502

AN - SCOPUS:85018305805

SN - 0021-9541

VL - 232

SP - 3664

EP - 3676

JO - Journal of Cellular Physiology

JF - Journal of Cellular Physiology

IS - 12

ER -

Deubiquitinating enzyme USP22 positively regulates c-Myc stability and tumorigenic activity in mammalian and breast cancer cells

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this