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

doi:10.1210/me.2015-1083

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Novel CARM1-Interacting Protein, DZIP3, Is a Transcriptional Coactivator of Estrogen Receptor-α

Journal article

Open access

Peer reviewed

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 and David Y Lee

Molecular endocrinology (Baltimore, Md.), Vol.29(12), pp.1708-1719

2015-12

DOI: https://doi.org/10.1210/me.2015-1083

PMCID: PMC4664229

PMID: 26505218

Abstract

Animals

Carrier Proteins - genetics

Carrier Proteins - metabolism

Cell Line

COS Cells

Estrogen Receptor alpha - genetics

Estrogen Receptor alpha - metabolism

Humans

Mice

Mice, Knockout

Nerve Tissue Proteins - genetics

Nerve Tissue Proteins - metabolism

Protein Binding - genetics

Protein Binding - physiology

Protein Binding - radiation effects

Protein-Arginine N-Methyltransferases - genetics

Protein-Arginine N-Methyltransferases - metabolism

RNA-Binding Proteins - genetics

RNA-Binding Proteins - metabolism

Transcriptional Activation - genetics

Transcriptional Activation - physiology

Ubiquitin-Protein Ligases - genetics

Ubiquitin-Protein Ligases - metabolism

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)-interacting 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 synergistically 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 ERα target genes. These results indicate that DZIP3 is a novel coactivator of ERα target gene expression.

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Collaboration types: Domestic collaboration
Citation topics: 1 Clinical & Life Sciences; 1.54 Molecular & Cell Biology - Genetics; 1.54.100 DNA Methylation
Web Of Science research areas: Endocrinology & Metabolism
ESI research areas: Biology & Biochemistry

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Title: Novel CARM1-Interacting Protein, DZIP3, Is a Transcriptional Coactivator of Estrogen Receptor-α
Creators: Daniel J Purcell - Section of Radiation Oncology (D.J.P., S.C., D.J.-S., K.R.E., T.D.T., D.Y.L.), Division of Hematology-Oncology, Department of Internal Medicine, and University of New Mexico Comprehensive Cancer Center, University of New Mexico School of Medicine, Albuquerque, New Mexico 87131; Department of Biochemistry (Y.-H.L.), Keck School of Medicine, University of Southern California. Los Angeles, California 90089; and Department of Radiation Oncology (B.M.), William Beaumont Hospital, Royal Oak, Michigan 48073
Swati Chauhan - Section of Radiation Oncology (D.J.P., S.C., D.J.-S., K.R.E., T.D.T., D.Y.L.), Division of Hematology-Oncology, Department of Internal Medicine, and University of New Mexico Comprehensive Cancer Center, University of New Mexico School of Medicine, Albuquerque, New Mexico 87131; Department of Biochemistry (Y.-H.L.), Keck School of Medicine, University of Southern California. Los Angeles, California 90089; and Department of Radiation Oncology (B.M.), William Beaumont Hospital, Royal Oak, Michigan 48073
Diane Jimenez-Stinson - Section of Radiation Oncology (D.J.P., S.C., D.J.-S., K.R.E., T.D.T., D.Y.L.), Division of Hematology-Oncology, Department of Internal Medicine, and University of New Mexico Comprehensive Cancer Center, University of New Mexico School of Medicine, Albuquerque, New Mexico 87131; Department of Biochemistry (Y.-H.L.), Keck School of Medicine, University of Southern California. Los Angeles, California 90089; and Department of Radiation Oncology (B.M.), William Beaumont Hospital, Royal Oak, Michigan 48073
Kathleen R Elliott - Section of Radiation Oncology (D.J.P., S.C., D.J.-S., K.R.E., T.D.T., D.Y.L.), Division of Hematology-Oncology, Department of Internal Medicine, and University of New Mexico Comprehensive Cancer Center, University of New Mexico School of Medicine, Albuquerque, New Mexico 87131; Department of Biochemistry (Y.-H.L.), Keck School of Medicine, University of Southern California. Los Angeles, California 90089; and Department of Radiation Oncology (B.M.), William Beaumont Hospital, Royal Oak, Michigan 48073
Tenzin D Tsewang - Section of Radiation Oncology (D.J.P., S.C., D.J.-S., K.R.E., T.D.T., D.Y.L.), Division of Hematology-Oncology, Department of Internal Medicine, and University of New Mexico Comprehensive Cancer Center, University of New Mexico School of Medicine, Albuquerque, New Mexico 87131; Department of Biochemistry (Y.-H.L.), Keck School of Medicine, University of Southern California. Los Angeles, California 90089; and Department of Radiation Oncology (B.M.), William Beaumont Hospital, Royal Oak, Michigan 48073
Young-Ho Lee - Section of Radiation Oncology (D.J.P., S.C., D.J.-S., K.R.E., T.D.T., D.Y.L.), Division of Hematology-Oncology, Department of Internal Medicine, and University of New Mexico Comprehensive Cancer Center, University of New Mexico School of Medicine, Albuquerque, New Mexico 87131; Department of Biochemistry (Y.-H.L.), Keck School of Medicine, University of Southern California. Los Angeles, California 90089; and Department of Radiation Oncology (B.M.), William Beaumont Hospital, Royal Oak, Michigan 48073
Brian Marples - Section of Radiation Oncology (D.J.P., S.C., D.J.-S., K.R.E., T.D.T., D.Y.L.), Division of Hematology-Oncology, Department of Internal Medicine, and University of New Mexico Comprehensive Cancer Center, University of New Mexico School of Medicine, Albuquerque, New Mexico 87131; Department of Biochemistry (Y.-H.L.), Keck School of Medicine, University of Southern California. Los Angeles, California 90089; and Department of Radiation Oncology (B.M.), William Beaumont Hospital, Royal Oak, Michigan 48073
David Y Lee - Section of Radiation Oncology (D.J.P., S.C., D.J.-S., K.R.E., T.D.T., D.Y.L.), Division of Hematology-Oncology, Department of Internal Medicine, and University of New Mexico Comprehensive Cancer Center, University of New Mexico School of Medicine, Albuquerque, New Mexico 87131; Department of Biochemistry (Y.-H.L.), Keck School of Medicine, University of Southern California. Los Angeles, California 90089; and Department of Radiation Oncology (B.M.), William Beaumont Hospital, Royal Oak, Michigan 48073
Publication Details: Molecular endocrinology (Baltimore, Md.), Vol.29(12), pp.1708-1719
Grant note: P30 CA118100 / NCI NIH HHS 5P30CA118100 / NCI NIH HHS
Language: English
Resource Type: Journal article
PMID: 26505218
PMCID: PMC4664229
Record Identifier: 991031614389202976