Cyclin D1 represses p300 transactivation through a cyclin-dependent kinase-independent mechanism

Maofu Fu, Chenguang Wang, Mahadev Rao, Xiaofang Wu, Toula Bouras, Xueping Zhang, Zhiping Li, Xuanmao Jiao, Jianguo Yang, Anping Li, Neil D. Perkins, Bayar Thimmapaya, Andrew L. Kung, Alberto Munoz, Antonio Giordano, Michael P. Lisanti, Richard G. Pestell

Research output: Contribution to journalArticle

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Abstract

Cyclin D1 encodes a regulatory subunit, which with its cyclin-dependent kinase (Cdk)-binding partner forms a holoenzyme that phosphorylates and inactivates the retinoblastoma protein. In addition to its Cdk binding-dependent functions, cyclin D1 regulates cellular differentiation in part by modifying several transcription factors and nuclear receptors. The molecular mechanism through which cyclin D1 regulates the function of transcription factors involved in cellular differentiation remains to be clarified. The histone acetyltransferase protein p300 is a co-integrator required for regulation of multiple transcription factors. Here we show that cyclin D1 physically interacts with p300 and represses p300 transactivation. We demonstrated further that the interaction of the two proteins occurs at the peroxisome proliferator-activated receptor γ-responsive element of the lipoprotein lipase promoter in the context of the local chromatin structure. We have mapped the domains in p300 and cyclin D1 involved in this interaction. The bromo domain and cysteine- and histidine-rich domains of p300 were required for repression by cyclin D1. Cyclin D1 repression of p300 was independent of the Cdk- and retinoblastoma protein-binding domains of cyclin D1. Cyclin D1 inhibits histone acetyltransferase activity of p300 in vitro. Microarray analysis identified a signature of genes repressed by cyclin D1 and induced by p300 that promotes cellular differentiation and induces cell cycle arrest. Together, our results suggest that cyclin D1 plays an important role in cellular proliferation and differentiation through regulation of p300.

Original languageEnglish
Pages (from-to)29728-29742
Number of pages15
JournalJournal of Biological Chemistry
Volume280
Issue number33
DOIs
Publication statusPublished - 19-08-2005

Fingerprint

Cyclin-Dependent Kinases
Cyclin D1
Transcriptional Activation
Histone Acetyltransferases
Retinoblastoma Protein
Transcription Factors
Retinoblastoma Binding Proteins
bcl-1 Genes
Holoenzymes
Peroxisome Proliferator-Activated Receptors
Lipoprotein Lipase
Microarray Analysis
Cytoplasmic and Nuclear Receptors
Cell Cycle Checkpoints
Histidine
Microarrays
Chromatin
Cysteine
Proteins
Cell Proliferation

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Fu, Maofu ; Wang, Chenguang ; Rao, Mahadev ; Wu, Xiaofang ; Bouras, Toula ; Zhang, Xueping ; Li, Zhiping ; Jiao, Xuanmao ; Yang, Jianguo ; Li, Anping ; Perkins, Neil D. ; Thimmapaya, Bayar ; Kung, Andrew L. ; Munoz, Alberto ; Giordano, Antonio ; Lisanti, Michael P. ; Pestell, Richard G. / Cyclin D1 represses p300 transactivation through a cyclin-dependent kinase-independent mechanism. In: Journal of Biological Chemistry. 2005 ; Vol. 280, No. 33. pp. 29728-29742.
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abstract = "Cyclin D1 encodes a regulatory subunit, which with its cyclin-dependent kinase (Cdk)-binding partner forms a holoenzyme that phosphorylates and inactivates the retinoblastoma protein. In addition to its Cdk binding-dependent functions, cyclin D1 regulates cellular differentiation in part by modifying several transcription factors and nuclear receptors. The molecular mechanism through which cyclin D1 regulates the function of transcription factors involved in cellular differentiation remains to be clarified. The histone acetyltransferase protein p300 is a co-integrator required for regulation of multiple transcription factors. Here we show that cyclin D1 physically interacts with p300 and represses p300 transactivation. We demonstrated further that the interaction of the two proteins occurs at the peroxisome proliferator-activated receptor γ-responsive element of the lipoprotein lipase promoter in the context of the local chromatin structure. We have mapped the domains in p300 and cyclin D1 involved in this interaction. The bromo domain and cysteine- and histidine-rich domains of p300 were required for repression by cyclin D1. Cyclin D1 repression of p300 was independent of the Cdk- and retinoblastoma protein-binding domains of cyclin D1. Cyclin D1 inhibits histone acetyltransferase activity of p300 in vitro. Microarray analysis identified a signature of genes repressed by cyclin D1 and induced by p300 that promotes cellular differentiation and induces cell cycle arrest. Together, our results suggest that cyclin D1 plays an important role in cellular proliferation and differentiation through regulation of p300.",
author = "Maofu Fu and Chenguang Wang and Mahadev Rao and Xiaofang Wu and Toula Bouras and Xueping Zhang and Zhiping Li and Xuanmao Jiao and Jianguo Yang and Anping Li and Perkins, {Neil D.} and Bayar Thimmapaya and Kung, {Andrew L.} and Alberto Munoz and Antonio Giordano and Lisanti, {Michael P.} and Pestell, {Richard G.}",
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Fu, M, Wang, C, Rao, M, Wu, X, Bouras, T, Zhang, X, Li, Z, Jiao, X, Yang, J, Li, A, Perkins, ND, Thimmapaya, B, Kung, AL, Munoz, A, Giordano, A, Lisanti, MP & Pestell, RG 2005, 'Cyclin D1 represses p300 transactivation through a cyclin-dependent kinase-independent mechanism', Journal of Biological Chemistry, vol. 280, no. 33, pp. 29728-29742. https://doi.org/10.1074/jbc.M503188200

Cyclin D1 represses p300 transactivation through a cyclin-dependent kinase-independent mechanism. / Fu, Maofu; Wang, Chenguang; Rao, Mahadev; Wu, Xiaofang; Bouras, Toula; Zhang, Xueping; Li, Zhiping; Jiao, Xuanmao; Yang, Jianguo; Li, Anping; Perkins, Neil D.; Thimmapaya, Bayar; Kung, Andrew L.; Munoz, Alberto; Giordano, Antonio; Lisanti, Michael P.; Pestell, Richard G.

In: Journal of Biological Chemistry, Vol. 280, No. 33, 19.08.2005, p. 29728-29742.

Research output: Contribution to journalArticle

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T1 - Cyclin D1 represses p300 transactivation through a cyclin-dependent kinase-independent mechanism

AU - Fu, Maofu

AU - Wang, Chenguang

AU - Rao, Mahadev

AU - Wu, Xiaofang

AU - Bouras, Toula

AU - Zhang, Xueping

AU - Li, Zhiping

AU - Jiao, Xuanmao

AU - Yang, Jianguo

AU - Li, Anping

AU - Perkins, Neil D.

AU - Thimmapaya, Bayar

AU - Kung, Andrew L.

AU - Munoz, Alberto

AU - Giordano, Antonio

AU - Lisanti, Michael P.

AU - Pestell, Richard G.

PY - 2005/8/19

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N2 - Cyclin D1 encodes a regulatory subunit, which with its cyclin-dependent kinase (Cdk)-binding partner forms a holoenzyme that phosphorylates and inactivates the retinoblastoma protein. In addition to its Cdk binding-dependent functions, cyclin D1 regulates cellular differentiation in part by modifying several transcription factors and nuclear receptors. The molecular mechanism through which cyclin D1 regulates the function of transcription factors involved in cellular differentiation remains to be clarified. The histone acetyltransferase protein p300 is a co-integrator required for regulation of multiple transcription factors. Here we show that cyclin D1 physically interacts with p300 and represses p300 transactivation. We demonstrated further that the interaction of the two proteins occurs at the peroxisome proliferator-activated receptor γ-responsive element of the lipoprotein lipase promoter in the context of the local chromatin structure. We have mapped the domains in p300 and cyclin D1 involved in this interaction. The bromo domain and cysteine- and histidine-rich domains of p300 were required for repression by cyclin D1. Cyclin D1 repression of p300 was independent of the Cdk- and retinoblastoma protein-binding domains of cyclin D1. Cyclin D1 inhibits histone acetyltransferase activity of p300 in vitro. Microarray analysis identified a signature of genes repressed by cyclin D1 and induced by p300 that promotes cellular differentiation and induces cell cycle arrest. Together, our results suggest that cyclin D1 plays an important role in cellular proliferation and differentiation through regulation of p300.

AB - Cyclin D1 encodes a regulatory subunit, which with its cyclin-dependent kinase (Cdk)-binding partner forms a holoenzyme that phosphorylates and inactivates the retinoblastoma protein. In addition to its Cdk binding-dependent functions, cyclin D1 regulates cellular differentiation in part by modifying several transcription factors and nuclear receptors. The molecular mechanism through which cyclin D1 regulates the function of transcription factors involved in cellular differentiation remains to be clarified. The histone acetyltransferase protein p300 is a co-integrator required for regulation of multiple transcription factors. Here we show that cyclin D1 physically interacts with p300 and represses p300 transactivation. We demonstrated further that the interaction of the two proteins occurs at the peroxisome proliferator-activated receptor γ-responsive element of the lipoprotein lipase promoter in the context of the local chromatin structure. We have mapped the domains in p300 and cyclin D1 involved in this interaction. The bromo domain and cysteine- and histidine-rich domains of p300 were required for repression by cyclin D1. Cyclin D1 repression of p300 was independent of the Cdk- and retinoblastoma protein-binding domains of cyclin D1. Cyclin D1 inhibits histone acetyltransferase activity of p300 in vitro. Microarray analysis identified a signature of genes repressed by cyclin D1 and induced by p300 that promotes cellular differentiation and induces cell cycle arrest. Together, our results suggest that cyclin D1 plays an important role in cellular proliferation and differentiation through regulation of p300.

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