ASK1-signaling promotes c-Myc protein stability during apoptosis

Kohji Noguchi, Akiko Kokubu, Chifumi Kitanaka, Hidenori Ichijo, Yoshiyuki Kuchino

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

We previously reported that JNK is involved in the regulation of c-Myc-mediated apoptosis triggered by UV irradiation and anticancer drug treatment. Here we show that ASK1 is an upstream regulator for c-Myc-mediated apoptosis triggered by UV, and we found a direct role for Ser-62 and Ser-71 in the regulation of protein stability and function of c-Myc. The ASK1-JNK pathway enhanced the protein stability of c-Myc through phosphorylation at Ser-62 and Ser-71, which was required for c-Myc-dependent apoptosis by ASK1-signaling. Interestingly, ASK1-signaling attenuated the degradation of ubiquitinated c-Myc without affecting the ubiquitination process. Together, these findings indicate that the ASK1-JNK pathway promotes the proapoptotic activity of c-Myc by modulating c-Myc protein stability through phosphorylation at Ser-62 and Ser-71.

Original languageEnglish
Pages (from-to)1313-1320
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume281
Issue number5
DOIs
Publication statusPublished - 2001
Externally publishedYes

Fingerprint

Proto-Oncogene Proteins c-myc
Protein Stability
Phosphorylation
MAP Kinase Signaling System
Apoptosis
Drug therapy
Ubiquitination
Proteins
Irradiation
Degradation
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

ASK1-signaling promotes c-Myc protein stability during apoptosis. / Noguchi, Kohji; Kokubu, Akiko; Kitanaka, Chifumi; Ichijo, Hidenori; Kuchino, Yoshiyuki.

In: Biochemical and Biophysical Research Communications, Vol. 281, No. 5, 2001, p. 1313-1320.

Research output: Contribution to journalArticle

Noguchi, K, Kokubu, A, Kitanaka, C, Ichijo, H & Kuchino, Y 2001, 'ASK1-signaling promotes c-Myc protein stability during apoptosis', Biochemical and Biophysical Research Communications, vol. 281, no. 5, pp. 1313-1320. https://doi.org/10.1006/bbrc.2001.4498
Noguchi, Kohji ; Kokubu, Akiko ; Kitanaka, Chifumi ; Ichijo, Hidenori ; Kuchino, Yoshiyuki. / ASK1-signaling promotes c-Myc protein stability during apoptosis. In: Biochemical and Biophysical Research Communications. 2001 ; Vol. 281, No. 5. pp. 1313-1320.
@article{955c5b0744034472add0dcd40b1d994f,
title = "ASK1-signaling promotes c-Myc protein stability during apoptosis",
abstract = "We previously reported that JNK is involved in the regulation of c-Myc-mediated apoptosis triggered by UV irradiation and anticancer drug treatment. Here we show that ASK1 is an upstream regulator for c-Myc-mediated apoptosis triggered by UV, and we found a direct role for Ser-62 and Ser-71 in the regulation of protein stability and function of c-Myc. The ASK1-JNK pathway enhanced the protein stability of c-Myc through phosphorylation at Ser-62 and Ser-71, which was required for c-Myc-dependent apoptosis by ASK1-signaling. Interestingly, ASK1-signaling attenuated the degradation of ubiquitinated c-Myc without affecting the ubiquitination process. Together, these findings indicate that the ASK1-JNK pathway promotes the proapoptotic activity of c-Myc by modulating c-Myc protein stability through phosphorylation at Ser-62 and Ser-71.",
author = "Kohji Noguchi and Akiko Kokubu and Chifumi Kitanaka and Hidenori Ichijo and Yoshiyuki Kuchino",
year = "2001",
doi = "10.1006/bbrc.2001.4498",
language = "English",
volume = "281",
pages = "1313--1320",
journal = "Biochemical and Biophysical Research Communications",
issn = "0006-291X",
publisher = "Academic Press Inc.",
number = "5",

}

TY - JOUR

T1 - ASK1-signaling promotes c-Myc protein stability during apoptosis

AU - Noguchi, Kohji

AU - Kokubu, Akiko

AU - Kitanaka, Chifumi

AU - Ichijo, Hidenori

AU - Kuchino, Yoshiyuki

PY - 2001

Y1 - 2001

N2 - We previously reported that JNK is involved in the regulation of c-Myc-mediated apoptosis triggered by UV irradiation and anticancer drug treatment. Here we show that ASK1 is an upstream regulator for c-Myc-mediated apoptosis triggered by UV, and we found a direct role for Ser-62 and Ser-71 in the regulation of protein stability and function of c-Myc. The ASK1-JNK pathway enhanced the protein stability of c-Myc through phosphorylation at Ser-62 and Ser-71, which was required for c-Myc-dependent apoptosis by ASK1-signaling. Interestingly, ASK1-signaling attenuated the degradation of ubiquitinated c-Myc without affecting the ubiquitination process. Together, these findings indicate that the ASK1-JNK pathway promotes the proapoptotic activity of c-Myc by modulating c-Myc protein stability through phosphorylation at Ser-62 and Ser-71.

AB - We previously reported that JNK is involved in the regulation of c-Myc-mediated apoptosis triggered by UV irradiation and anticancer drug treatment. Here we show that ASK1 is an upstream regulator for c-Myc-mediated apoptosis triggered by UV, and we found a direct role for Ser-62 and Ser-71 in the regulation of protein stability and function of c-Myc. The ASK1-JNK pathway enhanced the protein stability of c-Myc through phosphorylation at Ser-62 and Ser-71, which was required for c-Myc-dependent apoptosis by ASK1-signaling. Interestingly, ASK1-signaling attenuated the degradation of ubiquitinated c-Myc without affecting the ubiquitination process. Together, these findings indicate that the ASK1-JNK pathway promotes the proapoptotic activity of c-Myc by modulating c-Myc protein stability through phosphorylation at Ser-62 and Ser-71.

UR - http://www.scopus.com/inward/record.url?scp=0034805077&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034805077&partnerID=8YFLogxK

U2 - 10.1006/bbrc.2001.4498

DO - 10.1006/bbrc.2001.4498

M3 - Article

C2 - 11243879

AN - SCOPUS:0034805077

VL - 281

SP - 1313

EP - 1320

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

SN - 0006-291X

IS - 5

ER -