Hes6 controls cell proliferation via interaction with cAMP-response element-binding protein-binding protein in the promyelocytic leukemia nuclear body

Bokkee Eun, Yool Lee, Soontaek Hong, Jaesang Kim, Han Woong Lee, Kyungjin Kim, Woong Sun, Hyun Kim

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Hes6 is a basic helix-loop-helix transcription factor that functions in the differentiation of pluripotent progenitor cells and during tumorigenesis. However, the molecular mechanism for its function is largely unknown. Here we show that Hes6 is a component of the promyelocytic leukemia nuclear body (PML-NB) complex in the nuclei and that Hes6 inhibits cell proliferation through induction of p21 cyclin-dependent kinase inhibitor. We further show that Hes6 directly interacts with CREB-binding protein (CBP), one of the key components of PML-NB, via its basic domain. This association is critical for p21 induction through multiple mechanisms, including chromatin remodeling and p53 acetylation. Taken together, these results suggest that the Hes6-CBP complex in PML-NB may influence the proliferation of cells via p53-dependent and-independent pathways.

Original languageEnglish
Pages (from-to)5939-5949
Number of pages11
JournalJournal of Biological Chemistry
Volume283
Issue number9
DOIs
Publication statusPublished - 2008 Feb 29

Fingerprint

CREB-Binding Protein
Cyclic AMP Response Element-Binding Protein
Cell proliferation
Protein Binding
Carrier Proteins
Leukemia
Cell Proliferation
Cyclin-Dependent Kinase Inhibitor p21
Basic Helix-Loop-Helix Transcription Factors
Acetylation
Chromatin
Chromatin Assembly and Disassembly
Association reactions
Carcinogenesis
Stem Cells

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Eun, Bokkee ; Lee, Yool ; Hong, Soontaek ; Kim, Jaesang ; Lee, Han Woong ; Kim, Kyungjin ; Sun, Woong ; Kim, Hyun. / Hes6 controls cell proliferation via interaction with cAMP-response element-binding protein-binding protein in the promyelocytic leukemia nuclear body. In: Journal of Biological Chemistry. 2008 ; Vol. 283, No. 9. pp. 5939-5949.
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Hes6 controls cell proliferation via interaction with cAMP-response element-binding protein-binding protein in the promyelocytic leukemia nuclear body. / Eun, Bokkee; Lee, Yool; Hong, Soontaek; Kim, Jaesang; Lee, Han Woong; Kim, Kyungjin; Sun, Woong; Kim, Hyun.

In: Journal of Biological Chemistry, Vol. 283, No. 9, 29.02.2008, p. 5939-5949.

Research output: Contribution to journalArticle

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AU - Eun, Bokkee

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AU - Kim, Jaesang

AU - Lee, Han Woong

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AB - Hes6 is a basic helix-loop-helix transcription factor that functions in the differentiation of pluripotent progenitor cells and during tumorigenesis. However, the molecular mechanism for its function is largely unknown. Here we show that Hes6 is a component of the promyelocytic leukemia nuclear body (PML-NB) complex in the nuclei and that Hes6 inhibits cell proliferation through induction of p21 cyclin-dependent kinase inhibitor. We further show that Hes6 directly interacts with CREB-binding protein (CBP), one of the key components of PML-NB, via its basic domain. This association is critical for p21 induction through multiple mechanisms, including chromatin remodeling and p53 acetylation. Taken together, these results suggest that the Hes6-CBP complex in PML-NB may influence the proliferation of cells via p53-dependent and-independent pathways.

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