Estrogen receptor-α binds p53 tumor suppressor protein directly and represses its function

Wensheng Liu, Santhi D. Konduri, Sanjay Bansal, Bijaya K. Nayak, Sigrid A. Rajasekaran, Sankunny M. Karuppayil, Ayyappan K. Rajasekaran, Gokul M. Das

Research output: Contribution to journalArticle

109 Citations (Scopus)

Abstract

Estrogen receptor-α (ERα) promotes proliferation of breast cancer cells, whereas tumor suppressor protein p53 impedes proliferation of cells with genomic damage. Whether there is a direct link between these two antagonistic pathways has remained unclear. Here we report that ERα binds directly to p53 and represses its function. The activation function-2 (AF-2) domain of ERα and the C-terminal regulatory domain of p53 are necessary for the interaction. Knocking down p53 and ERα by small interfering RNA elicits opposite effects on p53-target gene expression and cell cycle progression. Remarkably, ionizing radiation that causes genomic damage disrupts the interaction between ERα and p53. Ionizing radiation together with ERα knock down results in an additive effect on transcription of endogenous p53-target gene p21 (CDKN1) in human breast cancer cells. Our findings reveal a novel mechanism for regulating p53 and suggest that suppressing p53 function is an important component in the pro-proliferative role of ERα.

Original languageEnglish (US)
Pages (from-to)9837-9840
Number of pages4
JournalJournal of Biological Chemistry
Volume281
Issue number15
DOIs
StatePublished - Apr 14 2006
Externally publishedYes

Fingerprint

Tumor Suppressor Protein p53
Estrogen Receptors
Ionizing radiation
p53 Genes
Cells
Ionizing Radiation
Breast Neoplasms
Transcription
Gene expression
Small Interfering RNA
Cell Cycle
Genes
Chemical activation
Cell Proliferation
Gene Expression

ASJC Scopus subject areas

  • Biochemistry

Cite this

Liu, W., Konduri, S. D., Bansal, S., Nayak, B. K., Rajasekaran, S. A., Karuppayil, S. M., ... Das, G. M. (2006). Estrogen receptor-α binds p53 tumor suppressor protein directly and represses its function. Journal of Biological Chemistry, 281(15), 9837-9840. https://doi.org/10.1074/jbc.C600001200

Estrogen receptor-α binds p53 tumor suppressor protein directly and represses its function. / Liu, Wensheng; Konduri, Santhi D.; Bansal, Sanjay; Nayak, Bijaya K.; Rajasekaran, Sigrid A.; Karuppayil, Sankunny M.; Rajasekaran, Ayyappan K.; Das, Gokul M.

In: Journal of Biological Chemistry, Vol. 281, No. 15, 14.04.2006, p. 9837-9840.

Research output: Contribution to journalArticle

Liu, W, Konduri, SD, Bansal, S, Nayak, BK, Rajasekaran, SA, Karuppayil, SM, Rajasekaran, AK & Das, GM 2006, 'Estrogen receptor-α binds p53 tumor suppressor protein directly and represses its function', Journal of Biological Chemistry, vol. 281, no. 15, pp. 9837-9840. https://doi.org/10.1074/jbc.C600001200
Liu W, Konduri SD, Bansal S, Nayak BK, Rajasekaran SA, Karuppayil SM et al. Estrogen receptor-α binds p53 tumor suppressor protein directly and represses its function. Journal of Biological Chemistry. 2006 Apr 14;281(15):9837-9840. https://doi.org/10.1074/jbc.C600001200
Liu, Wensheng ; Konduri, Santhi D. ; Bansal, Sanjay ; Nayak, Bijaya K. ; Rajasekaran, Sigrid A. ; Karuppayil, Sankunny M. ; Rajasekaran, Ayyappan K. ; Das, Gokul M. / Estrogen receptor-α binds p53 tumor suppressor protein directly and represses its function. In: Journal of Biological Chemistry. 2006 ; Vol. 281, No. 15. pp. 9837-9840.
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