WW domain binding protein-2, an E6-associated protein interacting protein, acts as a coactivator of estrogen and progesterone receptors

Sarath C. Dhananjayan, Sivapriya Ramamoorthy, Obaid Y. Khan, Ayesha Ismail, Jun Sun, Joyce M Slingerland, Bert W. O'Malley, Zafar Nawaz

Research output: Contribution to journalArticle

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Abstract

WW domain binding protein-2 (WBP-2) was cloned as an E6-associated protein interacting protein, and its role in steroid hormone receptors functions was investigated. We show that WBP-2 specifically enhanced the transactivation functions of progesterone receptor (PR) and estrogen receptor (ER), whereas it did not have any significant effect on the androgen receptor, glucocorticoid receptor, or the activation functions of p53 and VP-16. Depletion of endogenous WBP-2 with small interfering RNAs indicated that WBP-2 was required for the proper functioning of PR and ER. We also demonstrated that WBP-2 contains an intrinsic activation domain. Moreover, chromatin immunoprecipitation assays demonstrate the hormone-dependent recruitment of WBP-2 onto an estrogen-responsive promoter. Mutational analysis suggests that one of three polyproline (PY) motifs of WBP-2 is essential for its coactivation and intrinsic activation functions. We show that WBP-2 and E6-associated protein each enhance PR function, and their effect on PR action are additive when coexpressed, suggesting a common signaling pathway. In this study, we also demonstrate that the WBP-2 binding protein, Yes kinase-associated protein (YAP) enhances PR transactivation, but YAP's coactivation function is absolutely dependent on WBP-2. Taken together, our data establish the role of WBP-2 and YAP as coactivators for ER and PR transactivation pathways.

Original languageEnglish
Pages (from-to)2343-2354
Number of pages12
JournalMolecular Endocrinology
Volume20
Issue number10
DOIs
StatePublished - Oct 9 2006

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Progesterone Receptors
Estrogen Receptors
Carrier Proteins
Proteins
Transcriptional Activation
Protein Kinases
Hormones
Steroid Receptors
Chromatin Immunoprecipitation
Glucocorticoid Receptors
Androgen Receptors
Etoposide
Protein Binding
Small Interfering RNA
Estrogens

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism

Cite this

WW domain binding protein-2, an E6-associated protein interacting protein, acts as a coactivator of estrogen and progesterone receptors. / Dhananjayan, Sarath C.; Ramamoorthy, Sivapriya; Khan, Obaid Y.; Ismail, Ayesha; Sun, Jun; Slingerland, Joyce M; O'Malley, Bert W.; Nawaz, Zafar.

In: Molecular Endocrinology, Vol. 20, No. 10, 09.10.2006, p. 2343-2354.

Research output: Contribution to journalArticle

Dhananjayan, Sarath C. ; Ramamoorthy, Sivapriya ; Khan, Obaid Y. ; Ismail, Ayesha ; Sun, Jun ; Slingerland, Joyce M ; O'Malley, Bert W. ; Nawaz, Zafar. / WW domain binding protein-2, an E6-associated protein interacting protein, acts as a coactivator of estrogen and progesterone receptors. In: Molecular Endocrinology. 2006 ; Vol. 20, No. 10. pp. 2343-2354.
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