Cdk5-mediated phosphorylation of c-Myc on Ser-62 is essential in transcriptional activation of cyclin B1 by cyclin G1

Ran Seo Haeng, Joon Kim, Sangwoo Bae, Jae Won Soh, Yun Sil Lee

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

It has been reported previously that cyclin G1 enables cells to overcome radiation-induced G2 arrest and increased cell death and that these effects are mediated by transcriptional activation of cyclin B1. In this study, we further investigated the mechanism by which cyclin G1 transcriptionally activates cyclin B1. Deletion or point mutations within the cyclin B1 promoter region revealed that the c-Myc binding site (E-box) is necessary for cyclin G1-mediated transcriptional activation of cyclin B1 to occur. In addition, the kinase activity of Cdk5 was increased by cyclin G1 overexpression, and Cdk5 directly phosphorylated c-Myc on Ser-62. Furthermore, cyclin G1 mediated increased radiosensitivity, and radiation-induced M phase arrest was attenuated when RNA interference of Cdk5 was treated. Taken together, the results of this study indicate that Cdk5 activation in cells that overexpress cyclin G1 leads to c-Myc phosphorylation on Ser-62, which is responsible for cyclin G1-mediated transcriptional activation of cyclin B1.

Original languageEnglish
Pages (from-to)15601-15610
Number of pages10
JournalJournal of Biological Chemistry
Volume283
Issue number23
DOIs
Publication statusPublished - 2008 Jun 6

Fingerprint

Cyclin G1
Cyclin B1
Phosphorylation
Transcriptional Activation
Chemical activation
Radiation
Sequence Deletion
Radiation Tolerance
Cell death
RNA Interference
Point Mutation
Genetic Promoter Regions
Cell Division
Cell Death
Phosphotransferases
Binding Sites
RNA

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Cdk5-mediated phosphorylation of c-Myc on Ser-62 is essential in transcriptional activation of cyclin B1 by cyclin G1. / Haeng, Ran Seo; Kim, Joon; Bae, Sangwoo; Soh, Jae Won; Lee, Yun Sil.

In: Journal of Biological Chemistry, Vol. 283, No. 23, 06.06.2008, p. 15601-15610.

Research output: Contribution to journalArticle

Haeng, Ran Seo ; Kim, Joon ; Bae, Sangwoo ; Soh, Jae Won ; Lee, Yun Sil. / Cdk5-mediated phosphorylation of c-Myc on Ser-62 is essential in transcriptional activation of cyclin B1 by cyclin G1. In: Journal of Biological Chemistry. 2008 ; Vol. 283, No. 23. pp. 15601-15610.
@article{20c420d4fc1a47b49f76c5ba8c99908d,
title = "Cdk5-mediated phosphorylation of c-Myc on Ser-62 is essential in transcriptional activation of cyclin B1 by cyclin G1",
abstract = "It has been reported previously that cyclin G1 enables cells to overcome radiation-induced G2 arrest and increased cell death and that these effects are mediated by transcriptional activation of cyclin B1. In this study, we further investigated the mechanism by which cyclin G1 transcriptionally activates cyclin B1. Deletion or point mutations within the cyclin B1 promoter region revealed that the c-Myc binding site (E-box) is necessary for cyclin G1-mediated transcriptional activation of cyclin B1 to occur. In addition, the kinase activity of Cdk5 was increased by cyclin G1 overexpression, and Cdk5 directly phosphorylated c-Myc on Ser-62. Furthermore, cyclin G1 mediated increased radiosensitivity, and radiation-induced M phase arrest was attenuated when RNA interference of Cdk5 was treated. Taken together, the results of this study indicate that Cdk5 activation in cells that overexpress cyclin G1 leads to c-Myc phosphorylation on Ser-62, which is responsible for cyclin G1-mediated transcriptional activation of cyclin B1.",
author = "Haeng, {Ran Seo} and Joon Kim and Sangwoo Bae and Soh, {Jae Won} and Lee, {Yun Sil}",
year = "2008",
month = "6",
day = "6",
doi = "10.1074/jbc.M800987200",
language = "English",
volume = "283",
pages = "15601--15610",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "23",

}

TY - JOUR

T1 - Cdk5-mediated phosphorylation of c-Myc on Ser-62 is essential in transcriptional activation of cyclin B1 by cyclin G1

AU - Haeng, Ran Seo

AU - Kim, Joon

AU - Bae, Sangwoo

AU - Soh, Jae Won

AU - Lee, Yun Sil

PY - 2008/6/6

Y1 - 2008/6/6

N2 - It has been reported previously that cyclin G1 enables cells to overcome radiation-induced G2 arrest and increased cell death and that these effects are mediated by transcriptional activation of cyclin B1. In this study, we further investigated the mechanism by which cyclin G1 transcriptionally activates cyclin B1. Deletion or point mutations within the cyclin B1 promoter region revealed that the c-Myc binding site (E-box) is necessary for cyclin G1-mediated transcriptional activation of cyclin B1 to occur. In addition, the kinase activity of Cdk5 was increased by cyclin G1 overexpression, and Cdk5 directly phosphorylated c-Myc on Ser-62. Furthermore, cyclin G1 mediated increased radiosensitivity, and radiation-induced M phase arrest was attenuated when RNA interference of Cdk5 was treated. Taken together, the results of this study indicate that Cdk5 activation in cells that overexpress cyclin G1 leads to c-Myc phosphorylation on Ser-62, which is responsible for cyclin G1-mediated transcriptional activation of cyclin B1.

AB - It has been reported previously that cyclin G1 enables cells to overcome radiation-induced G2 arrest and increased cell death and that these effects are mediated by transcriptional activation of cyclin B1. In this study, we further investigated the mechanism by which cyclin G1 transcriptionally activates cyclin B1. Deletion or point mutations within the cyclin B1 promoter region revealed that the c-Myc binding site (E-box) is necessary for cyclin G1-mediated transcriptional activation of cyclin B1 to occur. In addition, the kinase activity of Cdk5 was increased by cyclin G1 overexpression, and Cdk5 directly phosphorylated c-Myc on Ser-62. Furthermore, cyclin G1 mediated increased radiosensitivity, and radiation-induced M phase arrest was attenuated when RNA interference of Cdk5 was treated. Taken together, the results of this study indicate that Cdk5 activation in cells that overexpress cyclin G1 leads to c-Myc phosphorylation on Ser-62, which is responsible for cyclin G1-mediated transcriptional activation of cyclin B1.

UR - http://www.scopus.com/inward/record.url?scp=47049104369&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=47049104369&partnerID=8YFLogxK

U2 - 10.1074/jbc.M800987200

DO - 10.1074/jbc.M800987200

M3 - Article

VL - 283

SP - 15601

EP - 15610

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 23

ER -