Novel CARM1-interacting protein, DZIP3, is a transcriptional coactivator of estrogen receptor-α

Daniel J. Purcell, Swati Chauhan, Diane Jimenez-Stinson, Kathleen R. Elliott, Tenzin D. Tsewang, Young Ho Lee, Brian Marples, David Y. Lee

Research output: Contribution to journalArticle

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Abstract

Coactivator-associated arginine methyltransferase 1 (CARM1) is known to promote estrogen receptor (ER)α-mediated transcription in breast cancer cells. To further characterize the regulation of ERα-mediated transcription by CARM1, we screened CARM1-interacting proteins by yeast two-hybrid. Here, we have identified an E3 ubiquitin ligase, DAZ (deleted in azoospermia)-inter-acting protein 3 (DZIP3), as a novel CARM1-binding protein. DZIP3-dependent ubiquitination of histone H2A has been associated with repression of transcription. However, ERα reporter gene assays demonstrated that DZIP3 enhanced ERα-mediated transcription and cooperated synergis-tically with CARM1. Interaction with CARM1 was observed with the E3 ligase RING domain of DZIP3. The methyltransferase activity of CARM1 partially contributed to the synergy with DZIP3 for transcription activation, but the E3 ubiquitin ligase activity of DZIP3 was dispensable. DZIP3 also interacted with the C-terminal activation domain 2 of glucocorticoid receptor-interacting protein 1 (GRIP1) and enhanced the interaction between GRIP1 and CARM1. Depletion of DZIP3 by small interfering RNA in MCF7 cells reduced estradiol-induced gene expression of ERα target genes, GREB1 and pS2, and DZIP3 was recruited to the estrogen response elements of the same ERa target genes. These results indicate that DZIP3 is a novel coactivator of ERα target gene expression.

Original languageEnglish (US)
Pages (from-to)1708-1719
Number of pages12
JournalMolecular Endocrinology
Volume29
Issue number12
DOIs
StatePublished - Dec 1 2015
Externally publishedYes

Fingerprint

Azoospermia
Estrogen Receptors
Proteins
Ubiquitin-Protein Ligases
Nuclear Receptor Coactivator 2
human DAZ1 protein
coactivator-associated arginine methyltransferase 1
Gene Expression
Fungal Proteins
Ubiquitination
MCF-7 Cells
Methyltransferases
Response Elements
Reporter Genes
Histones
Small Interfering RNA
Transcriptional Activation
Genes
Estradiol
Carrier Proteins

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

Cite this

Purcell, D. J., Chauhan, S., Jimenez-Stinson, D., Elliott, K. R., Tsewang, T. D., Lee, Y. H., ... Lee, D. Y. (2015). Novel CARM1-interacting protein, DZIP3, is a transcriptional coactivator of estrogen receptor-α. Molecular Endocrinology, 29(12), 1708-1719. https://doi.org/10.1210/me.2015-1083

Novel CARM1-interacting protein, DZIP3, is a transcriptional coactivator of estrogen receptor-α. / Purcell, Daniel J.; Chauhan, Swati; Jimenez-Stinson, Diane; Elliott, Kathleen R.; Tsewang, Tenzin D.; Lee, Young Ho; Marples, Brian; Lee, David Y.

In: Molecular Endocrinology, Vol. 29, No. 12, 01.12.2015, p. 1708-1719.

Research output: Contribution to journalArticle

Purcell, DJ, Chauhan, S, Jimenez-Stinson, D, Elliott, KR, Tsewang, TD, Lee, YH, Marples, B & Lee, DY 2015, 'Novel CARM1-interacting protein, DZIP3, is a transcriptional coactivator of estrogen receptor-α', Molecular Endocrinology, vol. 29, no. 12, pp. 1708-1719. https://doi.org/10.1210/me.2015-1083
Purcell DJ, Chauhan S, Jimenez-Stinson D, Elliott KR, Tsewang TD, Lee YH et al. Novel CARM1-interacting protein, DZIP3, is a transcriptional coactivator of estrogen receptor-α. Molecular Endocrinology. 2015 Dec 1;29(12):1708-1719. https://doi.org/10.1210/me.2015-1083
Purcell, Daniel J. ; Chauhan, Swati ; Jimenez-Stinson, Diane ; Elliott, Kathleen R. ; Tsewang, Tenzin D. ; Lee, Young Ho ; Marples, Brian ; Lee, David Y. / Novel CARM1-interacting protein, DZIP3, is a transcriptional coactivator of estrogen receptor-α. In: Molecular Endocrinology. 2015 ; Vol. 29, No. 12. pp. 1708-1719.
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