Aldose Reductase Acts as a Selective Derepressor of PPARγ and the Retinoic Acid Receptor

Thiagarajan, Devi; Ananthakrishnan, Radha; Zhang, Jinghua; O’Shea, Karen M.; Quadri, Nosirudeen; Li, Qing; Sas, Kelli M.; Xiao, Jing; Rosario, Rosa; Pennathur, Subramaniam; Schmidt, Ann Marie; Ramasamy, Ravichandran

doi:10.1016/j.celrep.2016.02.086

Cited by 24 publications

(19 citation statements)

References 92 publications

(109 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Of note, HDAC3 requires binding to the DAD domain of either NCOR1 or SMRT for its enzymatic function, indicating that NCOR1 regulates recruitment as well as the activity of HDAC3. The importance of NCOR1‐HDAC3 interactions for the regulation of cellular function has been reported in many biological processes including development, metabolism, and glucocorticoid receptor signaling . Apart from HDAC3, NCOR1 can also interact with class II HDACs (HDAC 4, 5, 7) as well as with HDAC1 in combination with the Sin3 repressor complex, thus broadening the spectrum of HDACs recruited to NCOR1 target genes.…”

Section: Basic Facts About Ncor1mentioning

confidence: 99%

NCOR1—a new player on the field of T cell development

Müller

Hainberger

Stolz

et al. 2018

Journal of Leukocyte Biology

View full text Add to dashboard Cite

Nuclear receptor corepressor 1 (NCOR1) is a transcriptional corepressor that links chromatin-modifying enzymes with gene-specific transcription factors. Although identified more than 20 years ago as a corepressor of nuclear receptors, the role of NCOR1 in T cells remained only poorly understood. However, recent studies indicate that the survival of developing thymocytes is regulated by NCOR1, revealing an essential role for NCOR1 in the T cell lineage. In this review, we will briefly summarize basic facts about NCOR1 structure and functions. We will further summarize studies demonstrating an essential role for NCOR1 in controlling positive and negative selection of thymocytes during T cell development. Finally, we will discuss similarities and differences between the phenotypes of mice with a T cell-specific deletion of NCOR1 or histone deacetylase 3 (HDAC3), because HDAC3 is the predominant member of the HDAC family that interacts with NCOR1 corepressor complexes. With this review we aim to introduce NCOR1 as a new player in the team of transcriptional coregulators that control T cell development and thus the generation of the peripheral T cell pool.

show abstract

Section: Basic Facts About Ncor1mentioning

confidence: 99%

NCOR1—a new player on the field of T cell development

Müller

Hainberger

Stolz

et al. 2018

Journal of Leukocyte Biology

View full text Add to dashboard Cite

show abstract

“…In our recent study [181], we showed that the interaction of polyol pathway enzyme aldose reductase (AR) with the nuclear corepressors, NCOR1 and SMRT, could lead to HDAC3 degradration (Figure 2). HDAC3, a class I enzyme exists as a multiprotein complex including HDAC3, nuclear corepressors and cofactors.…”

Section: Novel Mechanisms Impacting Hdac Functionmentioning

confidence: 99%

“…HDAC3 binds to the deacetylation domain (DAD) of either silencing mediator of retinoic and thyroid receptor (SMRT) or nuclear corepressor 1 (NCOR1) [176, 182]. Molecular, cellular, and in vivo studies revealed that AR interaction with the DAD domain of nuclear corepressors drives HDAC3 degradation, consequently leading to the expression of nuclear corepressor’s cofactors including Gps2 , Tblr1 , PPARγ activation and lipid accumulation in the hearts [181]. Our studies demonstrated that regulating the levels of nuclear corepressors or its cofactors could also result in changes of HDACs and consequently transcription.…”

Section: Novel Mechanisms Impacting Hdac Functionmentioning

confidence: 99%

See 1 more Smart Citation

Mechanisms of transcription factor acetylation and consequences in hearts

Thiagarajan

Vedantham

Ananthakrishnan

et al. 2016

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

Self Cite

View full text Add to dashboard Cite

Acetylation of proteins as a post-translational modification is gaining rapid acceptance as a cellular control mechanism on par with other protein modification mechanisms such as phosphorylation and ubiquitination. Through genetic manipulations and evolving proteomic technologies, identification and consequences of transcription factor acetylation is beginning to emerge. In this review, we summarize the field and discuss newly unfolding mechanisms and consequences of transcription factor acetylation in normal and stressed hearts.

show abstract

“…The Rev-erbα gene regulates the circadian rhythm to bind site in the BMAL1 gene promoter. The expression of BMAL1 protein is negatively correlated with the mRNA level of Rev-erbα [14][15]. On the other hand, HDAC3 activity contributes to ischemic cardiac damage [16].…”

Section: Introductionmentioning

confidence: 99%

Roles of HDAC3-Orchestrated Circadian Clock Gene Oscillations in Diabetic Rats Following Myocardial Ischemia / Reperfusion Injury

et al. 2020

View full text Add to dashboard Cite

Background: Circadian clock has been closely related to the development of diabetes mellitus and cardiovascular disease; the disruption of circadian clock exacerbates myocardial ischemia/reperfusion injury (MI/RI). HDAC3 is a key component of the circadian negative feedback loop by recruitmenting the expression pattern of circadian nuclear receptor Rev-erbα, then to maintain the stability of circadian gene such as BMAL1. In this research, we explored the mechanism of HDAC3-orchestrated Rev-erbα/BMAL1 pathway in increasing MI/RI vulnerability of diabetes, and its relationship with mitophagy. Methods and results: Streptozocin (STZ) was used to establish type 1 diabetes by intraperitoneal injection. After 8 weeks, the diabetic and non-diabetic rats were exposed to MI/RI by ligating the left anterior descending coronary artery (LDA) for 30 minutes and reperfusion for 120 minutes at four time points of zeitgeber (ZT) 0, 6, 12 and 18. Circadian clock gene oscillations were rapidly attenuated in diabetic I/RI hearts, versus sham and/or the non-diabetic I/RI hearts, in accord with circadian mitophagy. By utilizing AAV-HDAC3 to knockdown HDAC3 expression, HDAC3 deficiency significantly attenuated diabetic MI/RI associated with increased autophagy activation. In vitro experiments, primary cardiomyocytes with or without HDAC3 siRNA and Rev-erbα siRNA exposed to hypoxia/reoxygenation (H/R). The expression of HDAC3 and Rev-erbα in cardiomyocytes was increased under high glucose condition with decreased BMAL1 expression and autophagy level. After H/R stimulation, the cell injury was obviously increased with upregulated HDAC3 and Rev-erbα expression and decreased BMAL1 level. Moreover, high glucose aggravated H/R injury compared with low glucose by reducing autophagy level, increasing the levels of HDAC3 and Rev-erbα and down-regulating BMAL1 expression. HDAC3 and Rev-erbα siRNA can alleviate high glucose and H/R-induced injury by up-regulating BMAL1 expression and mitophagy levels. Conclusion: These findings suggest that in diabetic rat MI/RI , the circadian clocks were rapidly impaired then to inhibit mitophagy; cardiac-targeted manipulation of HDAC3-orchestrated Rev-erbα/BMAL1 pathway may be the mechanism of the decreased toleration to ischemia with a circadian dependent variability.

show abstract

Aldose Reductase Acts as a Selective Derepressor of PPARγ and the Retinoic Acid Receptor

Cited by 24 publications

References 92 publications

NCOR1—a new player on the field of T cell development

NCOR1—a new player on the field of T cell development

Mechanisms of transcription factor acetylation and consequences in hearts

Roles of HDAC3-Orchestrated Circadian Clock Gene Oscillations in Diabetic Rats Following Myocardial Ischemia / Reperfusion Injury

Contact Info

Product

Resources

About