Activated Notch1 interacts with p53 to inhibit its phosphorylation and transactivation

S. B. Kim; G. W. Chae; J. Lee; J. Park; H. Tak; J. H. Chung; T. G. Park; J. K. Ahn; C. O. Joe

doi:10.1038/sj.cdd.4402083

Activated Notch1 interacts with p53 to inhibit its phosphorylation and transactivation

S. B. Kim, G. W. Chae, J. Lee, J. Park, H. Tak, J. H. Chung, T. G. Park, J. K. Ahn, C. O. Joe

Research output: Contribution to journal › Article › peer-review

51 Scopus citations

Abstract

We propose a biochemical mechanism for the negative role of Notch signaling on p53 transactivation function. Expression of the intracellular domain of human Notch1 (Notch1-IC) inhibits the expression of p53-responsive genes p21, mdm2, and bax in HCT116 p53^-/- cells. Furthermore, Notch1-IC expression inhibits the phosphorylation of ectopically expressed p53 in HCT116 p53^-/- cells as well as the phosphorylation of endogenous p53 in UV-treated HCT116 p53^+/+ cells. Transcriptional downregulation of p53-responsive genes by Notch1-IC was confirmed both by chromatin immunoprecipitation assay and Northern blot analysis. We found the intracellular interaction between Notch1-IC and p53 in HCT116 p53^+/+ cells and suggest that activated Notch1 interaction with p53 is an important cellular event for the inhibition of p53-dependent transactivation. The N-terminal fragment of Notch1-IC, which can interacts with p53, inhibits p53 phosphorylation and represses p53 transactivation. In addition, Notch signaling downregulated p53-dependent apoptosis induced by UV irradiation.

Original language	English
Pages (from-to)	982-991
Number of pages	10
Journal	Cell Death and Differentiation
Volume	14
Issue number	5
DOIs	https://doi.org/10.1038/sj.cdd.4402083
State	Published - May 2007
Externally published	Yes

Funding

Acknowledgements. We are grateful to Dr. J Aster (Bringham and Women’s Hospital, USA) for providing pcDNA3-Notch1-IC expression plasmid. This study was supported in part by grants from the Korean National Cancer Control Program, Ministry of Health and Welfare (0220150-3); the Korea Science and Engineering Foundation (2004-01885); and the Korea Research Foundation (KRF-2003-015-C00534 and KRF-2005-070-C00105).

Funders	Funder number
Korea Research Foundation	KRF-2005-070-C00105, KRF-2003-015-C00534
Korean National Cancer Control Program
Ministry of Health and Welfare	0220150-3
Korea Science and Engineering Foundation	2004-01885

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title = "Activated Notch1 interacts with p53 to inhibit its phosphorylation and transactivation",

abstract = "We propose a biochemical mechanism for the negative role of Notch signaling on p53 transactivation function. Expression of the intracellular domain of human Notch1 (Notch1-IC) inhibits the expression of p53-responsive genes p21, mdm2, and bax in HCT116 p53-/- cells. Furthermore, Notch1-IC expression inhibits the phosphorylation of ectopically expressed p53 in HCT116 p53-/- cells as well as the phosphorylation of endogenous p53 in UV-treated HCT116 p53+/+ cells. Transcriptional downregulation of p53-responsive genes by Notch1-IC was confirmed both by chromatin immunoprecipitation assay and Northern blot analysis. We found the intracellular interaction between Notch1-IC and p53 in HCT116 p53+/+ cells and suggest that activated Notch1 interaction with p53 is an important cellular event for the inhibition of p53-dependent transactivation. The N-terminal fragment of Notch1-IC, which can interacts with p53, inhibits p53 phosphorylation and represses p53 transactivation. In addition, Notch signaling downregulated p53-dependent apoptosis induced by UV irradiation.",

author = "Kim, {S. B.} and Chae, {G. W.} and J. Lee and J. Park and H. Tak and Chung, {J. H.} and Park, {T. G.} and Ahn, {J. K.} and Joe, {C. O.}",

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AU - Kim, S. B.

AU - Chae, G. W.

AU - Lee, J.

AU - Park, J.

AU - Tak, H.

AU - Chung, J. H.

AU - Park, T. G.

AU - Ahn, J. K.

AU - Joe, C. O.

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N2 - We propose a biochemical mechanism for the negative role of Notch signaling on p53 transactivation function. Expression of the intracellular domain of human Notch1 (Notch1-IC) inhibits the expression of p53-responsive genes p21, mdm2, and bax in HCT116 p53-/- cells. Furthermore, Notch1-IC expression inhibits the phosphorylation of ectopically expressed p53 in HCT116 p53-/- cells as well as the phosphorylation of endogenous p53 in UV-treated HCT116 p53+/+ cells. Transcriptional downregulation of p53-responsive genes by Notch1-IC was confirmed both by chromatin immunoprecipitation assay and Northern blot analysis. We found the intracellular interaction between Notch1-IC and p53 in HCT116 p53+/+ cells and suggest that activated Notch1 interaction with p53 is an important cellular event for the inhibition of p53-dependent transactivation. The N-terminal fragment of Notch1-IC, which can interacts with p53, inhibits p53 phosphorylation and represses p53 transactivation. In addition, Notch signaling downregulated p53-dependent apoptosis induced by UV irradiation.

AB - We propose a biochemical mechanism for the negative role of Notch signaling on p53 transactivation function. Expression of the intracellular domain of human Notch1 (Notch1-IC) inhibits the expression of p53-responsive genes p21, mdm2, and bax in HCT116 p53-/- cells. Furthermore, Notch1-IC expression inhibits the phosphorylation of ectopically expressed p53 in HCT116 p53-/- cells as well as the phosphorylation of endogenous p53 in UV-treated HCT116 p53+/+ cells. Transcriptional downregulation of p53-responsive genes by Notch1-IC was confirmed both by chromatin immunoprecipitation assay and Northern blot analysis. We found the intracellular interaction between Notch1-IC and p53 in HCT116 p53+/+ cells and suggest that activated Notch1 interaction with p53 is an important cellular event for the inhibition of p53-dependent transactivation. The N-terminal fragment of Notch1-IC, which can interacts with p53, inhibits p53 phosphorylation and represses p53 transactivation. In addition, Notch signaling downregulated p53-dependent apoptosis induced by UV irradiation.

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Activated Notch1 interacts with p53 to inhibit its phosphorylation and transactivation

Abstract

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