Cyclin D1 Is a Ligand-independent Co-repressor for Thyroid Hormone Receptors

Lin, Huei-Min; Zhao, Li; Cheng, Sheue-yann

doi:10.1074/jbc.m203380200

Cited by 85 publications

(64 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In addition, recent evidence suggests that cyclin D1 antagonizes the activity of the transcription factor, C/EBPb, in a cell cycle-independent fashion to contribute to the oncogenesis observed in overexpressing mammary carcinoma cells (Lamb et al, 2003). In contrast to its action in driving mammary oncogenesis and function as an ERa coactivator, cyclin D1 also acts as a potent corepressor of TRb1, PPARg, and AR (Lin et al, 2002;.…”

Section: Introductionmentioning

confidence: 99%

“…Subsequently, it was demonstrated that cyclin D1 can bind to HDAC3 and recruit this repressor molecule to the TRb1 complex (Lin et al, 2002). Given our observation that the repressor domain is sufficient for corepressor activity, we hypothesized that HDAC3 may bind to this region of cyclin D1.…”

Section: Cyclin D1 Repressor Domain Is Sufficient For Ar Binding and mentioning

confidence: 99%

“…Specifically, cyclin D1 has been linked to the regulation of ERa, TRb1, PPARg, and AR (Neuman et al, 1997;Zwijsen et al, 1997Zwijsen et al, , 1998Knudsen et al, 1999;Lin et al, 2002;Petre et al, 2002;Petre-Draviam et al, 2003;. Although the response of these receptors to cyclin D1 action is varied, they are each highly regulated by association with their respective ligands.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

A central domain of cyclin D1 mediates nuclear receptor corepressor activity

et al. 2004

View full text Add to dashboard Cite

Regulation of nuclear receptor activity is the focus of numerous ongoing studies to develop novel therapies for the treatment of hormone-related cancer. Although cyclin D1 functions to control the activity of several nuclear receptors, the region(s) of the protein responsible for such transcriptional comodulation remain poorly defined. Herein, we map the region of cyclin D1 required for binding and repression of the androgen receptor (AR) to a central, exclusively a-helical domain. Deletion of this domain disrupted AR binding and corepressor activity. Further investigations showed that this domain is sufficient for AR interaction and possesses the ability to bind histone deacetylase 3. Strikingly, overexpression of this repressor region attenuates cell cycle progression in prostatic adenocarcinoma cells. The requirement of this domain for nuclear receptor repression was conserved with respect to thyroid hormone receptor beta-1, whereas cyclin D1 activation of the estrogen receptor occurred independently of the central region. Together, these data identify a minimal repression module within cyclin D1 and demonstrate that the coactivator and corepressor functions of cyclin D1 are distinct. In addition, our data suggest that properties of the cyclin D1 central domain could be exploited to develop novel prostate cancer therapeutics.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Cyclin D1 Repressor Domain Is Sufficient For Ar Binding and mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A central domain of cyclin D1 mediates nuclear receptor corepressor activity

et al. 2004

View full text Add to dashboard Cite

show abstract

“…In specific cell types, cyclin D1 is found in association with the estrogen receptor a, thyroid hormone receptor, peroxisome proliferatoractivated receptor-g and the androgen receptor (AR) (Neuman et al, 1997;Zwijsen et al, 1998;Knudsen et al, 1999;Reutens et al, 2001;Lin et al, 2002;Petre et al, 2002;Petre-Draviam et al, 2003;Wang et al, 2003;Burd et al, 2005). With estrogen receptor, cyclin D1 can potentiate receptor activity independently of ligand and CDK4-kinase activity (Neuman et al, 1997), through formation of a ternary complex with estrogen receptor a and P/CAF, thereby altering chromatin structure to facilitate gene transcription (McMahon et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

“…Mechanisms are attributed to a discrete repressor domain, which binds to the AR N-terminus and prevents ligand-dependent conformational changes in AR . Additionally, this motif can recruit histone deacetylase 3 (HDAC3), and the AR-repressor function of cyclin D1 is dependent on HDAC function (Lin et al, 2002;Petre et al, 2002;Petre-Draviam et al, 2005). Concordantly, the repressor domain of cyclin D1 is also required for cyclin D1-mediated suppression of peroxisome proliferator-activated receptor-g activity (Fu et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Cyclin D3 action in androgen receptor regulation and prostate cancer

et al. 2007

View full text Add to dashboard Cite

Prostate cancer (PCa) cell proliferation is dependent on activation of the androgen receptor (AR), a liganddependent transcription factor. AR activation controls G1-S phase progression through fostering enhanced translation of the D-type cyclins, which promote cell cycle progression through activation of CDK4/6. However, the D-type cyclins harbor additional, CDK4/6 kinase-independent, functions through manipulation of transcription factors, including AR. It was previously established that cyclins D1 and D3 have the potential to modulate AR, and with regard to cyclin D1, disruption of this function occurs in human tumors. Therefore, it was essential to interrogate cyclin D3 function in this tumor type. Here, we show that cyclin D3 is found in association with AR in PCa cells, as mediated through a conserved motif. Cyclin D3 functions to attenuate AR activity through defined mechanisms that include modulation of ligand-dependent conformational changes and modulation of chromatin binding activity. Accumulated cyclin D3 slows cell proliferation in AR-dependent cells, thus suggesting that androgen-induced D-type cyclin production serves to temper the mitogenic response to androgen. Supporting this hypothesis, it is shown that cyclin D3 expression is reduced in primary PCas as a function of tumor grade, and inversely correlates with the proliferative index. In total, these data identify cyclin D3 as a critical modulator of the androgen response, whose deregulation may foster unchecked AR activity in PCa.

show abstract

Thyroid hormones regulate DNA‐synthesis and cell‐cycle proteins by activation of PKCα and p42/44 MAPK in chick embryo hepatocytes

Alisi

Spagnuolo

Napoletano

et al. 2004

Journal Cellular Physiology

View full text Add to dashboard Cite

The molecular mechanism by which thyroid hormones exert their effects on cell growth is still unknown. In this study, we used chick embryo hepatocytes at different stages of development as a model to investigate the effect of the two thyroid hormones, T3 and T4, and of their metabolite T2, on the control of cell proliferation. We observed that T2 provokes increase of DNA-synthesis as well as T3 and T4, independently of developmental stage. We found that this stimulatory effect on the S phase is reverted by specific inhibitors of protein kinase C (PKC) and p42/44 mitogen-activated protein kinase (p42/44 MAPK), Ro 31-8220 or PD 98059. Furthermore, the treatment with thyroid hormones induces the activation of PKCalpha and p42/44 MAPK, suggesting their role as possible downstream mediators of cell response mediated by thyroid hormones. The increase of DNA-synthesis is well correlated with the increased levels of cyclin D1 and cdk4 that control the G1 phase, and also with the activities of cell-cycle proteins involved in the G1 to S phase progression, such as cyclin E/A-cdk2 complexes. Interestingly, the activity of cyclin-cdk2 complexes is strongly repressed in the presence of PKC and p42/44 MAPK inhibitors. In conclusion, we demonstrated that the thyroid hormones could modulate different signaling pathways that are able to control cell-cycle progression, mainly during G1/S transition.

show abstract

Cyclin D1 Is a Ligand-independent Co-repressor for Thyroid Hormone Receptors

Cited by 85 publications

References 36 publications

A central domain of cyclin D1 mediates nuclear receptor corepressor activity

A central domain of cyclin D1 mediates nuclear receptor corepressor activity

Cyclin D3 action in androgen receptor regulation and prostate cancer

Thyroid hormones regulate DNA‐synthesis and cell‐cycle proteins by activation of PKCα and p42/44 MAPK in chick embryo hepatocytes

Contact Info

Product

Resources

About