Deleted in Breast Cancer 1, a Novel Androgen Receptor (AR) Coactivator That Promotes AR DNA-binding Activity

Fu, Junjiang; Jiang, Jun; Li, Jiwen; Wang, Shanshan; Shi, Guang; Feng, Qin; White, Eileen; Qin, Jun; Wong, Jiemin

doi:10.1074/jbc.m808988200

Cited by 65 publications

(85 citation statements)

References 55 publications

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“…This mechanism, in turn, triggers an increase in lipid synthesis by the liver and the onset of the inflammatory response observed during fatty liver disease. DBC1 has also been recently shown to associate and regulate other targets such as the estrogen receptor, androgen receptor, and SUV39H1 methyltransferase (53)(54)(55). Whether the effects of DBC1 on these proteins have any physiological relevance or account for any of the phenotypes seen in our studies is not known and deserves further evaluation.…”

Section: Discussionmentioning

confidence: 61%

Deleted in breast cancer–1 regulates SIRT1 activity and contributes to high-fat diet–induced liver steatosis in mice

Escande¹,

Chini²,

Nin³

et al. 2010

J. Clin. Invest.

158

212

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The enzyme sirtuin 1 (SIRT1) is a critical regulator of many cellular functions, including energy metabolism. However, the precise mechanisms that modulate SIRT1 activity remain unknown. As SIRT1 activity in vitro was recently found to be negatively regulated by interaction with the deleted in breast cancer-1 (DBC1) protein, we set out to investigate whether DBC1 regulates SIRT1 activity in vivo. We found that DBC1 and SIRT1 colocalized and interacted, and that DBC1 modulated SIRT1 activity, in multiple cell lines and tissues. In mouse liver, increased SIRT1 activity, concomitant with decreased DBC1-SIRT1 interaction, was detected after 24 hours of starvation, whereas decreased SIRT1 activity and increased interaction with DBC1 was observed with high-fat diet (HFD) feeding. Consistent with the hypothesis that DBC1 is crucial for HFD-induced inhibition of SIRT1 and for the development of experimental liver steatosis, genetic deletion of Dbc1 in mice led to increased SIRT1 activity in several tissues, including liver. Furthermore, DBC1-deficient mice were protected from HFD-induced liver steatosis and inflammation, despite the development of obesity. These observations define what we believe to be a new role for DBC1 as an in vivo regulator of SIRT1 activity and liver steatosis. We therefore propose that the DBC1-SIRT1 interaction may serve as a new target for therapies aimed at nonalcoholic liver steatosis.

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Section: Discussionmentioning

confidence: 61%

Deleted in breast cancer–1 regulates SIRT1 activity and contributes to high-fat diet–induced liver steatosis in mice

Escande¹,

Chini²,

Nin³

et al. 2010

J. Clin. Invest.

158

212

View full text Add to dashboard Cite

show abstract

“…ChIP assays were performed using M2 Flag antibody beads and antibodies against TWIST, MTA2, HDAC2, RbBp46, Mi2b [49]. For ChIP-re-ChIP assays, the eluted materials were diluted with dilution buffer and subjected to the re-ChIP step using antibodies against MTA2, HDAC2 and Mi2β and the protein A/G beads.…”

Section: Chip and Chip-re-chip Assaysmentioning

confidence: 99%

“…Methods for immunoprecipitation (IP) and immunoblotting were described previously [47,49]. TrueBlot IP/WB kit from eBioscience was used to eliminate the IgG bands in the immunoblotting analysis.…”

Section: Immunoprecipitation and Immunoblottingmentioning

confidence: 99%

The TWIST/Mi2/NuRD protein complex and its essential role in cancer metastasis

et al. 2010

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The epithelial-mesenchymal transition (EMT) converts epithelial tumor cells into invasive and metastatic cancer cells, leading to mortality in cancer patients. Although TWIST is a master regulator of EMT and metastasis for breast and other cancers, the mechanisms responsible for TWIST-mediated gene transcription remain unknown. In this study, purification and characterization of the TWIST protein complex revealed that TWIST interacts with several components of the Mi2/nucleosome remodeling and deacetylase (Mi2/NuRD) complex, MTA2, RbAp46, Mi2 and HDAC2, and recruits them to the proximal regions of the E-cadherin promoter for transcriptional repression. Depletion of these TWIST complex components from cancer cell lines that depend on TWIST for metastasis efficiently suppresses cell migration and invasion in culture and lung metastasis in mice. These findings not only provide novel mechanistic and functional links between TWIST and the Mi2/NuRD complex but also establish new essential roles for the components of Mi2/NuRD complex in cancer metastasis.

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“…DBC1 induces p53-mediated apoptosis by negatively regulating silent mating type information regulation 2 homolog 1 (SIRT1) activity (6,7), and by directly interacting with estrogen receptor-α (ERα) promotes breast cancer cell survival (8). In addition, DBC1 regulates cancer cell growth by mediating the transcriptional activation of retinoic acid receptor α (RAR α) in breast cancer or androgen receptor (AR) in prostate cancer cells (9,10). DBC1 also regulates epigenetic mechanisms by inhibiting SUV39H1 methyltransferase and histone deacetylase 3 (HDAC3) (11,12).…”

Section: Introductionmentioning

confidence: 99%

DBC1 does not function as a negative regulator of SIRT1 in liver cancer

et al. 2012

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Abstract. The putative tumor suppressor, DBC1 (deleted in breast cancer-1), was recently found to negatively regulate SIRT1 in vitro and in vivo, but the mechanism whereby DBC1 regulates SIRT1 in liver cancer remains to be elucidated. In this study, it was found that although the expression of DBC1 and SIRT1 was not aberrantly regulated in a large cohort of human hepatocellular carcinoma (HCC) patients, these proteins were highly overexpressed in a subset of HCC tissues compared with surrounding non-cancer tissues. In liver cancer, DBC1 and SIRT1 were found to be positively correlated. Inactivation of DBC1 or SIRT1 reduced SNU-182 (a liver cancer cell line) proliferation as determined by MTT viability assays. Notably, although DBC1 functions as a negative regulator of SIRT1 in A549 lung cancer cells since it suppresses the deacetylase activity of the p53 protein, it did not affect the p53 deacetylase activity of SIRT1 in SNU-182 cells. Taken together, we conclude that DBC1 is associated with SIRT1 in HCC, but that it does not inhibit SIRT1.

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Deleted in Breast Cancer 1, a Novel Androgen Receptor (AR) Coactivator That Promotes AR DNA-binding Activity

Cited by 65 publications

References 55 publications

Deleted in breast cancer–1 regulates SIRT1 activity and contributes to high-fat diet–induced liver steatosis in mice

Deleted in breast cancer–1 regulates SIRT1 activity and contributes to high-fat diet–induced liver steatosis in mice

The TWIST/Mi2/NuRD protein complex and its essential role in cancer metastasis

DBC1 does not function as a negative regulator of SIRT1 in liver cancer

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