Activation of the cyclin D1 gene by the E1A-associated protein p300 through AP-1 inhibits cellular apoptosis

Chris Albanese, Mark D'Amico, Anne T. Reutens, Maofu Fu, Genichi Watanabe, Richard J. Lee, Richard N. Kitsis, Berthold Henglein, Maria Avantaggiati, Kumaravel Somasundaram, Bayar Thimmapaya, Richard G. Pestell

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Abstract

The adenovirus E1A protein interferes with regulators of apoptosis and growth by physically interacting with cell cycle regulatory proteins including the retinoblastoma tumor suppressor protein and the coactivator proteins p300/CBP (where CBP is the CREB-binding protein). The p300/CBP proteins occupy a pivotal role in regulating mitogenic signaling and apoptosis. The mechanisms by which cell cycle control genes are directly regulated by p300 remain to be determined. The cyclin D1 gene, which is overexpressed in many different tumor types, encodes a regulatory subunit of a holoenzyme that phosphorylates and inactivates PRB. In the present study E1A12S inhibited the cyclin D1 promoter via the amino-terminal p300/CBP binding domain in human choriocarcinoma JEG-3 cells, p300 induced cyclin D1 protein abundance, and p300, but not CBP, induced the cyclin D1 promoter, cyclin D1 or p300 overexpression inhibited apoptosis in JEG-3 cells. The CH3 region of p300, which was required for induction of cyclin D1, was also required for the inhibition of apoptosis. p300 activated the cyclin D1 promoter through an activator protein-1 (AP-1) site at -954 and was identified within a DNA-bound complex with c-Jun at the AP-1 site. Apoptosis rates of embryonic fibroblasts derived from mice homozygously deleted of the cyclin D1 gene (cyclin D1(-/-)) were increased compared with wild type control on several distinct matrices, p300 inhibited apoptosis in cyclin D1(+/+) fibroblasts but increased apoptosis in cyclin D1(-/-) cells. The anti-apoptotic function of cyclin D1, demonstrated by sub-G1 analysis and annexin V staining, may contribute to its cellular transforming and cooperative oncogenic properties.

Original languageEnglish (US)
Pages (from-to)34186-34195
Number of pages10
JournalJournal of Biological Chemistry
Volume274
Issue number48
DOIs
StatePublished - Nov 26 1999

Fingerprint

E1A-Associated p300 Protein
bcl-1 Genes
Cyclin D1
Transcription Factor AP-1
Genes
Chemical activation
Apoptosis
p300-CBP Transcription Factors
Adenovirus E1A Proteins
Fibroblasts
CREB-Binding Protein
Tumor Suppressor Proteins
cdc Genes
Retinoblastoma Protein
Cell Cycle Proteins
Holoenzymes
Choriocarcinoma
Annexin A5
Cell Cycle Checkpoints

ASJC Scopus subject areas

  • Biochemistry

Cite this

Albanese, C., D'Amico, M., Reutens, A. T., Fu, M., Watanabe, G., Lee, R. J., ... Pestell, R. G. (1999). Activation of the cyclin D1 gene by the E1A-associated protein p300 through AP-1 inhibits cellular apoptosis. Journal of Biological Chemistry, 274(48), 34186-34195. https://doi.org/10.1074/jbc.274.48.34186

Activation of the cyclin D1 gene by the E1A-associated protein p300 through AP-1 inhibits cellular apoptosis. / Albanese, Chris; D'Amico, Mark; Reutens, Anne T.; Fu, Maofu; Watanabe, Genichi; Lee, Richard J.; Kitsis, Richard N.; Henglein, Berthold; Avantaggiati, Maria; Somasundaram, Kumaravel; Thimmapaya, Bayar; Pestell, Richard G.

In: Journal of Biological Chemistry, Vol. 274, No. 48, 26.11.1999, p. 34186-34195.

Research output: Contribution to journalArticle

Albanese, C, D'Amico, M, Reutens, AT, Fu, M, Watanabe, G, Lee, RJ, Kitsis, RN, Henglein, B, Avantaggiati, M, Somasundaram, K, Thimmapaya, B & Pestell, RG 1999, 'Activation of the cyclin D1 gene by the E1A-associated protein p300 through AP-1 inhibits cellular apoptosis', Journal of Biological Chemistry, vol. 274, no. 48, pp. 34186-34195. https://doi.org/10.1074/jbc.274.48.34186
Albanese, Chris ; D'Amico, Mark ; Reutens, Anne T. ; Fu, Maofu ; Watanabe, Genichi ; Lee, Richard J. ; Kitsis, Richard N. ; Henglein, Berthold ; Avantaggiati, Maria ; Somasundaram, Kumaravel ; Thimmapaya, Bayar ; Pestell, Richard G. / Activation of the cyclin D1 gene by the E1A-associated protein p300 through AP-1 inhibits cellular apoptosis. In: Journal of Biological Chemistry. 1999 ; Vol. 274, No. 48. pp. 34186-34195.
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