The Coactivator p/CIP/SRC-3 Facilitates Retinoic Acid Receptor Signaling via Recruitment of GCN5

Brown, Kirk; Chen, Ying; Underhill, T. Michael; Mymryk, Joe S.; Torchia, Joseph

doi:10.1074/jbc.m307832200

Cited by 40 publications

(29 citation statements)

References 79 publications

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“…2A). This suggests that SUG-1 would contribute to RAR␣-dependent transcriptional activation as efficiency as SRC-3 (20,27). In contrast, knockdown of the other p160 coactivators, SRC-2 and SRC-1, had no effect (Fig.…”

Section: Sug-1 and Src-3 Contribute To The Transcription Of Ra Targetmentioning

confidence: 72%

SUG-1 Plays Proteolytic and Non-proteolytic Roles in the Control of Retinoic Acid Target Genes via Its Interaction with SRC-3

Ferry

Giannı̀

Lalevée

et al. 2009

Journal of Biological Chemistry

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Nuclear retinoic acid receptor ␣ (RAR␣) activates gene expression through dynamic interactions with coregulatory protein complexes, the assembly of which is directed by the ligand and the AF-2 domain of RAR␣. Then RAR␣ and its coactivator SRC-3 are degraded by the proteasome. Recently it has emerged that the proteasome also plays a key role in RAR␣-mediated transcription. Here we show that SUG-1, one of the six ATPases of the 19 S regulatory complex of the 26 S proteasome, interacts with SRC-3, is recruited at the promoters of retinoic acid (RA) target genes, and thereby participates to their transcription. In addition, SUG-1 also mediates the proteasomal degradation of SRC-3. However, when present in excess amounts, SUG-1 blocks the activation of RAR␣ target genes and the degradation of RAR␣ that occurs in response to RA, via its ability to interfere with the recruitment of SRC-3 and other coregulators at the AF-2 domain of RAR␣. We propose a model in which the ratio between SUG-1 and SRC-3 is crucial for the control of RAR␣ functioning. This study provides new insights into how SUG-1 has a unique role in linking the transcription and degradation processes via its ability to interact with SRC-3.

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Section: Sug-1 and Src-3 Contribute To The Transcription Of Ra Targetmentioning

confidence: 72%

SUG-1 Plays Proteolytic and Non-proteolytic Roles in the Control of Retinoic Acid Target Genes via Its Interaction with SRC-3

Ferry

Giannı̀

Lalevée

et al. 2009

Journal of Biological Chemistry

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“…Yeast assays can be designed also to study mechanisms of coactivator function. For example, phenotypes conferred upon expression of hSRC-3 (Brown et al, 2003), GRIP1 and SRC-1 (Anafi et al, 2000) revealed a role for Gcn5 HAT complex components. These and other ingenious yeast assays will lend further insight into mechanisms underlying human MYST HAT function.…”

mentioning

confidence: 99%

MYST opportunities for growth control: yeast genes illuminate human cancer gene functions

et al. 2007

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The MYST family of histone acetyltransferases (HATs) was initially defined by human genes with disease connections and by yeast genes identified for their role in epigenetic transcriptional silencing. Since then, many new MYST genes have been discovered through genetic and genomic approaches. Characterization of the complexes through which MYST proteins act, regions of the genome to which they are targeted and biological consequences when they are disrupted, all deepen the connections of MYST proteins to development, growth control and human cancers. Many of the insights into MYST family function have come from studies in model organisms. Herein, we review functions of two of the founding MYST genes, yeast SAS2 and SAS3, and the essential yeast MYST ESA1. Analysis of these genes in yeast has defined roles for MYST proteins in transcriptional activation and silencing, and chromatin-mediated boundary formation. They have further roles in DNA damage repair and nuclear integrity. The observation that MYST protein complexes share subunits with other HATs, histone deacetylases and other key nuclear proteins, many with connections to human cancers, strengthens the idea that coordinating distinct chromatin modifications is critical for regulation.

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“…It has been reported that retinoic acid receptor-dependent signaling is facilitated by SRC-3 (19). Following all trans-retinoic acid (ATRA) treatment, p38 MAPK is activated in metaplastic Barrett's cells (20), NB-4 human acute promyelocytic leukemia cell line, and MCF-7 human breast carcinoma cell line (21).…”

Section: Introductionmentioning

confidence: 99%

p38 Mitogen‐activated protein kinase‐dependent regulation of SRC‐3 and involvement in retinoic acid receptor α signaling in embryonic cortical neurons

Chai

Yang

et al. 2009

IUBMB Life

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Appropriate retinoic acid (RA) signaling is essential in the development of the central nervous system (CNS). Previous studies have shown that RA activates p38 mitogen‐activated protein kinase (MAPK) and steroid receptor coactivator (SRC)‐3 in tumor cells in vitro. It is unknown whether the activation of p38 MAPK and SRC‐3 is involved in RA‐mediated CNS development. The current study investigated a possible role for p38 MAPK in the regulation of (SRC)‐3 phosphorylation/degradation and in retinoic acid receptor (RAR)α signaling in mouse fetal cortical neurons treated with all‐trans retinoic acid (ATRA). Results showed that ATRA treatment rapidly activated p38 MAPK, which in turn resulted in phosphorylation with subsequent degradation of SRC‐3. Inhibition of p38 MAPK by SB203580 blocked the phosphorylation and degradation of SRC‐3. The binding of RARα to retinoic acid responsive element (RARE) was rapidly increased in neurons following ATRA treatment. Inhibition of p38 MAPK significantly enhanced the RARα‐RARE binding activity, but had no effects on ATRA‐induced decrease of RARα. Treatment of the fetal cortical neurons with ATRA significantly increased the expression of HOXd3, a retinoid‐target gene. The increase of HOXd3 expression was augmented when p38 MAPK activity was inhibited by a specific inhibitor, SB203580. Results suggest that ATRA activates the p38 MAPK signal pathway with resultant degradation of SRC‐3, and that p38 MAPK is involved in the regulation of RARα‐mediated signaling in developing neurons. © 2009 IUBMB IUBMB Life, 61(6): 670–678, 2009

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The Coactivator p/CIP/SRC-3 Facilitates Retinoic Acid Receptor Signaling via Recruitment of GCN5

Cited by 40 publications

References 79 publications

SUG-1 Plays Proteolytic and Non-proteolytic Roles in the Control of Retinoic Acid Target Genes via Its Interaction with SRC-3

SUG-1 Plays Proteolytic and Non-proteolytic Roles in the Control of Retinoic Acid Target Genes via Its Interaction with SRC-3

MYST opportunities for growth control: yeast genes illuminate human cancer gene functions

p38 Mitogen‐activated protein kinase‐dependent regulation of SRC‐3 and involvement in retinoic acid receptor α signaling in embryonic cortical neurons

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