GSK-3β regulates cyclin D1 expression: A new target for chemotherapy

Fumi Takahashi-Yanaga, Toshiyuki Sasaguri

Research output: Contribution to journalReview article

188 Citations (Scopus)

Abstract

Cyclin D1 is known as a proto-oncogene whose gene amplification and protein overexpression are frequently observed in tumor cells. It acts as a mitogenic signal sensor and is expressed as a delayed-early response to many mitogenic signals. Cyclin-dependent kinases (CDKs) 4 and 6 are cyclin D1 binding partners, and activated cyclin D1/CDK4 and cyclin D1/CDK6 complex phosphorylate the retinoblastoma protein to induce the expression of target genes essential for S phase entry, resulting in facilitation of the progression from G1 to S phase. As well as acting as a positive regulator of the cell cycle, cyclin D1 is known to bind and modulate the actions of several transcription factors. Since the protein level of cyclin D1 reflects cell cycle progression, the rates of protein production and degradation are strictly regulated. Glycogen synthase kinase-3β (GSK-3β), a serine/threonine protein kinase, has been shown to play an important role in the determination of cyclin D1 expression level by regulating mRNA transcription and protein degradation. This review highlights the regulatory mechanisms of cyclin D1 expression level, with special attention to the involvement of GSK-3β.

Original languageEnglish
Pages (from-to)581-589
Number of pages9
JournalCellular Signalling
Volume20
Issue number4
DOIs
Publication statusPublished - Apr 1 2008

Fingerprint

Glycogen Synthase Kinase 3
Cyclin D1
Drug Therapy
S Phase
Proteolysis
Cell Cycle
Cyclin-Dependent Kinase 6
Cyclin-Dependent Kinase 4
Retinoblastoma Protein
Proto-Oncogenes
Gene Amplification
Protein-Serine-Threonine Kinases
Essential Genes
RNA Stability
Proteins
Transcription Factors
Gene Expression

All Science Journal Classification (ASJC) codes

  • Cell Biology

Cite this

GSK-3β regulates cyclin D1 expression : A new target for chemotherapy. / Takahashi-Yanaga, Fumi; Sasaguri, Toshiyuki.

In: Cellular Signalling, Vol. 20, No. 4, 01.04.2008, p. 581-589.

Research output: Contribution to journalReview article

@article{afa8b54b9baa4f609d22107db0ffeb3f,
title = "GSK-3β regulates cyclin D1 expression: A new target for chemotherapy",
abstract = "Cyclin D1 is known as a proto-oncogene whose gene amplification and protein overexpression are frequently observed in tumor cells. It acts as a mitogenic signal sensor and is expressed as a delayed-early response to many mitogenic signals. Cyclin-dependent kinases (CDKs) 4 and 6 are cyclin D1 binding partners, and activated cyclin D1/CDK4 and cyclin D1/CDK6 complex phosphorylate the retinoblastoma protein to induce the expression of target genes essential for S phase entry, resulting in facilitation of the progression from G1 to S phase. As well as acting as a positive regulator of the cell cycle, cyclin D1 is known to bind and modulate the actions of several transcription factors. Since the protein level of cyclin D1 reflects cell cycle progression, the rates of protein production and degradation are strictly regulated. Glycogen synthase kinase-3β (GSK-3β), a serine/threonine protein kinase, has been shown to play an important role in the determination of cyclin D1 expression level by regulating mRNA transcription and protein degradation. This review highlights the regulatory mechanisms of cyclin D1 expression level, with special attention to the involvement of GSK-3β.",
author = "Fumi Takahashi-Yanaga and Toshiyuki Sasaguri",
year = "2008",
month = "4",
day = "1",
doi = "10.1016/j.cellsig.2007.10.018",
language = "English",
volume = "20",
pages = "581--589",
journal = "Cellular Signalling",
issn = "0898-6568",
publisher = "Elsevier Inc.",
number = "4",

}

TY - JOUR

T1 - GSK-3β regulates cyclin D1 expression

T2 - A new target for chemotherapy

AU - Takahashi-Yanaga, Fumi

AU - Sasaguri, Toshiyuki

PY - 2008/4/1

Y1 - 2008/4/1

N2 - Cyclin D1 is known as a proto-oncogene whose gene amplification and protein overexpression are frequently observed in tumor cells. It acts as a mitogenic signal sensor and is expressed as a delayed-early response to many mitogenic signals. Cyclin-dependent kinases (CDKs) 4 and 6 are cyclin D1 binding partners, and activated cyclin D1/CDK4 and cyclin D1/CDK6 complex phosphorylate the retinoblastoma protein to induce the expression of target genes essential for S phase entry, resulting in facilitation of the progression from G1 to S phase. As well as acting as a positive regulator of the cell cycle, cyclin D1 is known to bind and modulate the actions of several transcription factors. Since the protein level of cyclin D1 reflects cell cycle progression, the rates of protein production and degradation are strictly regulated. Glycogen synthase kinase-3β (GSK-3β), a serine/threonine protein kinase, has been shown to play an important role in the determination of cyclin D1 expression level by regulating mRNA transcription and protein degradation. This review highlights the regulatory mechanisms of cyclin D1 expression level, with special attention to the involvement of GSK-3β.

AB - Cyclin D1 is known as a proto-oncogene whose gene amplification and protein overexpression are frequently observed in tumor cells. It acts as a mitogenic signal sensor and is expressed as a delayed-early response to many mitogenic signals. Cyclin-dependent kinases (CDKs) 4 and 6 are cyclin D1 binding partners, and activated cyclin D1/CDK4 and cyclin D1/CDK6 complex phosphorylate the retinoblastoma protein to induce the expression of target genes essential for S phase entry, resulting in facilitation of the progression from G1 to S phase. As well as acting as a positive regulator of the cell cycle, cyclin D1 is known to bind and modulate the actions of several transcription factors. Since the protein level of cyclin D1 reflects cell cycle progression, the rates of protein production and degradation are strictly regulated. Glycogen synthase kinase-3β (GSK-3β), a serine/threonine protein kinase, has been shown to play an important role in the determination of cyclin D1 expression level by regulating mRNA transcription and protein degradation. This review highlights the regulatory mechanisms of cyclin D1 expression level, with special attention to the involvement of GSK-3β.

UR - http://www.scopus.com/inward/record.url?scp=39049107744&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=39049107744&partnerID=8YFLogxK

U2 - 10.1016/j.cellsig.2007.10.018

DO - 10.1016/j.cellsig.2007.10.018

M3 - Review article

C2 - 18023328

AN - SCOPUS:39049107744

VL - 20

SP - 581

EP - 589

JO - Cellular Signalling

JF - Cellular Signalling

SN - 0898-6568

IS - 4

ER -