ZNF313 is a novel cell cycle activator with an E3 ligase activity inhibiting cellular senescence by destabilizing p21WAF1

J. Han, Y. L. Kim, Kwang Won Lee, N. G. Her, T. K. Ha, S. Yoon, S. I. Jeong, J. H. Lee, M. J. Kang, M. G. Lee, B. K. Ryu, Ja-Hyun Baik, Sung-Gil Chi

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

ZNF313 encoding a zinc-binding protein is located at chromosome 20q13.13, which exhibits a frequent genomic amplification in multiple human cancers. However, the biological function of ZNF313 remains largely undefined. Here we report that ZNF313 is an ubiquitin E3 ligase that has a critical role in the regulation of cell cycle progression, differentiation and senescence. In this study, ZNF313 is initially identified as a XIAP-associated factor 1 (XAF1)-interacting protein, which upregulates the stability and proapoptotic effect of XAF1. Intriguingly, we found that ZNF313 activates cell cycle progression and suppresses cellular senescence through the RING domain-mediated degradation of p21WAF1. ZNF313 ubiquitinates p21WAF1 and also destabilizes p27KIP1 and p57KIP2, three members of the CDK-interacting protein (CIP)/kinase inhibitor protein (KIP) family of cyclin-dependent kinase inhibitors, whereas it does not affect the stability of the inhibitor of CDK (INK4) family members, such as p16INK4A and p15INK4B. ZNF313 expression is tightly controlled during the cell cycle and its elevation at the late G1 phase is crucial for the G1-to-S phase transition. ZNF313 is induced by mitogenic growth factors and its blockade profoundly delays cell cycle progression and accelerates p21WAF1 -mediated senescence. Both replicative and stress-induced senescence are accompanied with ZNF313 reduction. ZNF313 is downregulated during cellular differentiation process in vitro and in vivo, while it is commonly upregulated in many types of cancer cells. ZNF313 shows both the nuclear and cytoplasmic localization in epithelial cells of normal tissues, but exhibits an intense cytoplasmic distribution in carcinoma cells of tumor tissues. Collectively, ZNF313 is a novel E3 ligase for p21WAF1, whose alteration might be implicated in the pathogenesis of several human diseases, including cancers.

Original languageEnglish
Pages (from-to)1055-1067
Number of pages13
JournalCell Death and Differentiation
Volume20
Issue number8
DOIs
Publication statusPublished - 2013 Aug 1

Fingerprint

Ubiquitin-Protein Ligases
Cell Aging
Cell Cycle
Neoplasms
Cyclin-Dependent Kinase Inhibitor Proteins
Phase Transition
G1 Phase
Protein Kinase Inhibitors
S Phase
Intercellular Signaling Peptides and Proteins
Up-Regulation
Down-Regulation
Chromosomes
Epithelial Cells
Carcinoma
Proteins

Keywords

  • Apoptosis
  • CDK inhibitor
  • Differentiation
  • Ubiquitin ligase
  • XAF1

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

ZNF313 is a novel cell cycle activator with an E3 ligase activity inhibiting cellular senescence by destabilizing p21WAF1 . / Han, J.; Kim, Y. L.; Lee, Kwang Won; Her, N. G.; Ha, T. K.; Yoon, S.; Jeong, S. I.; Lee, J. H.; Kang, M. J.; Lee, M. G.; Ryu, B. K.; Baik, Ja-Hyun; Chi, Sung-Gil.

In: Cell Death and Differentiation, Vol. 20, No. 8, 01.08.2013, p. 1055-1067.

Research output: Contribution to journalArticle

Han, J. ; Kim, Y. L. ; Lee, Kwang Won ; Her, N. G. ; Ha, T. K. ; Yoon, S. ; Jeong, S. I. ; Lee, J. H. ; Kang, M. J. ; Lee, M. G. ; Ryu, B. K. ; Baik, Ja-Hyun ; Chi, Sung-Gil. / ZNF313 is a novel cell cycle activator with an E3 ligase activity inhibiting cellular senescence by destabilizing p21WAF1 In: Cell Death and Differentiation. 2013 ; Vol. 20, No. 8. pp. 1055-1067.
@article{25e41d09a03e4502a47eac42c8b9c034,
title = "ZNF313 is a novel cell cycle activator with an E3 ligase activity inhibiting cellular senescence by destabilizing p21WAF1",
abstract = "ZNF313 encoding a zinc-binding protein is located at chromosome 20q13.13, which exhibits a frequent genomic amplification in multiple human cancers. However, the biological function of ZNF313 remains largely undefined. Here we report that ZNF313 is an ubiquitin E3 ligase that has a critical role in the regulation of cell cycle progression, differentiation and senescence. In this study, ZNF313 is initially identified as a XIAP-associated factor 1 (XAF1)-interacting protein, which upregulates the stability and proapoptotic effect of XAF1. Intriguingly, we found that ZNF313 activates cell cycle progression and suppresses cellular senescence through the RING domain-mediated degradation of p21WAF1. ZNF313 ubiquitinates p21WAF1 and also destabilizes p27KIP1 and p57KIP2, three members of the CDK-interacting protein (CIP)/kinase inhibitor protein (KIP) family of cyclin-dependent kinase inhibitors, whereas it does not affect the stability of the inhibitor of CDK (INK4) family members, such as p16INK4A and p15INK4B. ZNF313 expression is tightly controlled during the cell cycle and its elevation at the late G1 phase is crucial for the G1-to-S phase transition. ZNF313 is induced by mitogenic growth factors and its blockade profoundly delays cell cycle progression and accelerates p21WAF1 -mediated senescence. Both replicative and stress-induced senescence are accompanied with ZNF313 reduction. ZNF313 is downregulated during cellular differentiation process in vitro and in vivo, while it is commonly upregulated in many types of cancer cells. ZNF313 shows both the nuclear and cytoplasmic localization in epithelial cells of normal tissues, but exhibits an intense cytoplasmic distribution in carcinoma cells of tumor tissues. Collectively, ZNF313 is a novel E3 ligase for p21WAF1, whose alteration might be implicated in the pathogenesis of several human diseases, including cancers.",
keywords = "Apoptosis, CDK inhibitor, Differentiation, Ubiquitin ligase, XAF1",
author = "J. Han and Kim, {Y. L.} and Lee, {Kwang Won} and Her, {N. G.} and Ha, {T. K.} and S. Yoon and Jeong, {S. I.} and Lee, {J. H.} and Kang, {M. J.} and Lee, {M. G.} and Ryu, {B. K.} and Ja-Hyun Baik and Sung-Gil Chi",
year = "2013",
month = "8",
day = "1",
doi = "10.1038/cdd.2013.33",
language = "English",
volume = "20",
pages = "1055--1067",
journal = "Cell Death and Differentiation",
issn = "1350-9047",
publisher = "Nature Publishing Group",
number = "8",

}

TY - JOUR

T1 - ZNF313 is a novel cell cycle activator with an E3 ligase activity inhibiting cellular senescence by destabilizing p21WAF1

AU - Han, J.

AU - Kim, Y. L.

AU - Lee, Kwang Won

AU - Her, N. G.

AU - Ha, T. K.

AU - Yoon, S.

AU - Jeong, S. I.

AU - Lee, J. H.

AU - Kang, M. J.

AU - Lee, M. G.

AU - Ryu, B. K.

AU - Baik, Ja-Hyun

AU - Chi, Sung-Gil

PY - 2013/8/1

Y1 - 2013/8/1

N2 - ZNF313 encoding a zinc-binding protein is located at chromosome 20q13.13, which exhibits a frequent genomic amplification in multiple human cancers. However, the biological function of ZNF313 remains largely undefined. Here we report that ZNF313 is an ubiquitin E3 ligase that has a critical role in the regulation of cell cycle progression, differentiation and senescence. In this study, ZNF313 is initially identified as a XIAP-associated factor 1 (XAF1)-interacting protein, which upregulates the stability and proapoptotic effect of XAF1. Intriguingly, we found that ZNF313 activates cell cycle progression and suppresses cellular senescence through the RING domain-mediated degradation of p21WAF1. ZNF313 ubiquitinates p21WAF1 and also destabilizes p27KIP1 and p57KIP2, three members of the CDK-interacting protein (CIP)/kinase inhibitor protein (KIP) family of cyclin-dependent kinase inhibitors, whereas it does not affect the stability of the inhibitor of CDK (INK4) family members, such as p16INK4A and p15INK4B. ZNF313 expression is tightly controlled during the cell cycle and its elevation at the late G1 phase is crucial for the G1-to-S phase transition. ZNF313 is induced by mitogenic growth factors and its blockade profoundly delays cell cycle progression and accelerates p21WAF1 -mediated senescence. Both replicative and stress-induced senescence are accompanied with ZNF313 reduction. ZNF313 is downregulated during cellular differentiation process in vitro and in vivo, while it is commonly upregulated in many types of cancer cells. ZNF313 shows both the nuclear and cytoplasmic localization in epithelial cells of normal tissues, but exhibits an intense cytoplasmic distribution in carcinoma cells of tumor tissues. Collectively, ZNF313 is a novel E3 ligase for p21WAF1, whose alteration might be implicated in the pathogenesis of several human diseases, including cancers.

AB - ZNF313 encoding a zinc-binding protein is located at chromosome 20q13.13, which exhibits a frequent genomic amplification in multiple human cancers. However, the biological function of ZNF313 remains largely undefined. Here we report that ZNF313 is an ubiquitin E3 ligase that has a critical role in the regulation of cell cycle progression, differentiation and senescence. In this study, ZNF313 is initially identified as a XIAP-associated factor 1 (XAF1)-interacting protein, which upregulates the stability and proapoptotic effect of XAF1. Intriguingly, we found that ZNF313 activates cell cycle progression and suppresses cellular senescence through the RING domain-mediated degradation of p21WAF1. ZNF313 ubiquitinates p21WAF1 and also destabilizes p27KIP1 and p57KIP2, three members of the CDK-interacting protein (CIP)/kinase inhibitor protein (KIP) family of cyclin-dependent kinase inhibitors, whereas it does not affect the stability of the inhibitor of CDK (INK4) family members, such as p16INK4A and p15INK4B. ZNF313 expression is tightly controlled during the cell cycle and its elevation at the late G1 phase is crucial for the G1-to-S phase transition. ZNF313 is induced by mitogenic growth factors and its blockade profoundly delays cell cycle progression and accelerates p21WAF1 -mediated senescence. Both replicative and stress-induced senescence are accompanied with ZNF313 reduction. ZNF313 is downregulated during cellular differentiation process in vitro and in vivo, while it is commonly upregulated in many types of cancer cells. ZNF313 shows both the nuclear and cytoplasmic localization in epithelial cells of normal tissues, but exhibits an intense cytoplasmic distribution in carcinoma cells of tumor tissues. Collectively, ZNF313 is a novel E3 ligase for p21WAF1, whose alteration might be implicated in the pathogenesis of several human diseases, including cancers.

KW - Apoptosis

KW - CDK inhibitor

KW - Differentiation

KW - Ubiquitin ligase

KW - XAF1

UR - http://www.scopus.com/inward/record.url?scp=84880296493&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84880296493&partnerID=8YFLogxK

U2 - 10.1038/cdd.2013.33

DO - 10.1038/cdd.2013.33

M3 - Article

C2 - 23645206

AN - SCOPUS:84880296493

VL - 20

SP - 1055

EP - 1067

JO - Cell Death and Differentiation

JF - Cell Death and Differentiation

SN - 1350-9047

IS - 8

ER -