The LIM protein Ajuba promotes adipogenesis by enhancing PPARγ and p300/CBP interaction

Li, Qingfeng; Peng, Hongzhuang; Fan, Huahao; Zou, Xinzhuo; Liu, Q; Zhang, Y; Xu, Hong; Chu, Yi-Min; Wang, C; Ayyanathan, Kasirajan; Rauscher, Frank J.; Zhang, K; Hou, Zhaoyuan

doi:10.1038/cdd.2015.83

Cited by 28 publications

(39 citation statements)

References 45 publications

(80 reference statements)

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“…The 3T3-L1 pre-adipocytes were cultured and differentiation was induced as previously described (23). The 3T3-L1 pre-adipocytes were cultured in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% bovine calf serum, penicillin (100 U/ml), streptomycin (100 µ g/ml) and glutamine (292 µ g/l).…”

Section: Methodsmentioning

confidence: 99%

Amentoflavone protects against high fat-induced metabolic dysfunction: Possible role of the regulation of adipogenic differentiation

Chen

Han

et al. 2016

International Journal of Molecular Medicine

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In the present study, we evaluated the protective effects of amentoflavone (AMF) against high-fat (HF) diet-induced metabolic dysfunction and focused on the influence of AMF on adipogenic differentiation during 3T3-L1 adipocyte differentiation. For this purpose, male Wistar rats were fed a HF diet or a HF diet with AMF (10 or 50 mg/kg). We found that AMF protected against HF diet-induced metabolic dysfunction in a dose-dependent manner, as evidenced by a decrease in the fasting blood glucose levels, fasting insulin levels and the homeostatic model assessment-insulin resistance index (HOMA-IR), as well as by a decrease in the glucose level, as shown by the intraperitoneal glucose tolerance test and intraperitoneal insulin tolerance test. Moreover, the results revealed that AMF significantly inhibited the increase in body weight, the weight of perirenal adipose tissues and the serum triglyceride (TG) content of the rats fed the HF diet in a dose-dependent manner. AMF also inhibited the accumulation of oil droplets in differentiated 3T3-L1 adipocytes in a concentration-dependent manner. The incubation of the cells with AMF for 0–8, 0–2, 2–4, or 4–8 days markedly inhibited adipogenesis. During the early phase of the adipocyte differentiation of 3T3-L1 cells, AMF decreased CCAAT/enhancer-binding protein (C/EBP) β expression in a concentration-dependent manner, leading to the inhibition of mitotic clonal expansion (MCE). Moreover, our results demonstrated that AMF significantly increased reactive oxygen species (ROS) generation in the cells and the antioxidant, N-acetylcysteine (NAC), markedly attenuated the inhibitory effects of AMF on adipogenesis. AMF also inhibited the expression of peroxisome proliferator-activated receptor γ (PPARγ) and C/EBPα and the expression of downstream targets in a concentration-dependent manner. The overexpression of PPARγ and C/EBPα (by transfection with respective overexpression plasmids) attentuated the inhibitory effects of AMF on the formation of oil droplets. The inhibitory effects of AMF on adipocyte differentiation may contribute to its protective effects against HF diet-induced metabolic dysfunction. Overall, the data in our study provide novel insight into the mechanisms responsible for the protective effects of AMF against HF diet-induced metabolic dysfunction and those for its inhibitory effect on adipocyte differentiation.

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Section: Methodsmentioning

confidence: 99%

Amentoflavone protects against high fat-induced metabolic dysfunction: Possible role of the regulation of adipogenic differentiation

Chen

Han

et al. 2016

International Journal of Molecular Medicine

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“…For example, HIC-5 acts as a co-activator for the androgen receptor 37 38 and for the GR 39 40 41 , and as a co-repressor for SMAD3 42 and the LEF/TCF transcription factors 43 . Similarly, AJUBA, which acts as a co-repressor for the transcriptional repressors SNAIL/SLUG 44 45 46 and GFI1 47 , was recently shown to act as a co-activator for PPARγ 48 and LXR 49 . How can the very same adaptor co-regulator mediate the recruitment of either a co-activator or a co-repressor?…”

Section: Discussionmentioning

confidence: 99%

“…As stated above, AJUBA also acts as either a co-activator or a co-repressor, depending on the transcription factor it interacts with. Interestingly, AJUBA interacts with SNAIL via its LIM domains 46 and mediates the recruitment of the PRMT5 co-repressor via its pre-LIM region 45 , whereas it interacts with PPARγ via its pre-LIM region and mediates the recruitment the p300/CBP co-activator via its LIM domains 48 . It is therefore tempting to speculate that the interaction with the transcription factors somehow affects the ability of the LIM domain protein to recruit either a co-activator or a co-repressor.…”

Section: Discussionmentioning

confidence: 99%

The LIM domain protein nTRIP6 acts as a co-repressor for the transcription factor MEF2C in myoblasts

Kemler

Dahley

Roßwag

et al. 2016

Sci Rep

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The transcription factor Myocyte enhancer factor 2C (MEF2C) plays a key role in the late differentiation of skeletal muscle progenitor cells, the so-called myoblasts. During myoblast differentiation, both MEF2C expression and transcriptional activity are regulated. We have reported that nTRIP6, the nuclear isoform of the focal adhesion LIM domain protein TRIP6, acts as an adaptor transcriptional co-activator for several transcription factors. It interacts with the promoter-bound transcription factors and consequently mediates the recruitment of other co-activators. Based on a described interaction between MEF2C and TRIP6 in a yeast-two-hybrid screen, we hypothesised a co-regulatory function of nTRIP6 for MEF2C. In proliferating myoblasts, nTRIP6 interacted with MEF2C and was recruited together with MEF2C to the MEF2-binding regions of the MEF2C target genes Myom2, Mb, Tnni2 and Des. Silencing nTRIP6 or preventing its interaction with MEF2C increased MEF2C transcriptional activity and increased the expression of these MEF2C target genes. Thus, nTRIP6 acts as a co-repressor for MEF2C. Mechanistically, nTRIP6 mediated the recruitment of the class IIa histone deacetylase HDAC5 to the MEF2C-bound promoters. In conclusion, our results unravel a transcriptional co-repressor function for nTRIP6. This adaptor co-regulator can thus exert either co-activator or co-repressor functions, depending on the transcription factor it interacts with.

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“…Stem Cells InternationalMultiple transcription factors are involved in the lineage selection and terminal differentiation of MSCs. Peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/ enhancer-binding proteins (C/EBPs), adipocyte assay and differentiation-dependent factor 1/sterol response elementbinding protein 1c (ADD1/SREBP1c) are key regulators of mammalian adipocyte differentiation and also participate in the spectrum selection and terminal differentiation of MSCs[62,63]. Studies have shown that the activation of PPARγ and C/EBPα is accomplished by the interaction of transcrip-tion factors, coactivators, and coinhibitors.…”

mentioning

confidence: 99%

Concise Review: The Regulatory Mechanism of Lysine Acetylation in Mesenchymal Stem Cell Differentiation

Yang

Liu

et al. 2020

Stem Cells International

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Nowadays, the use of MSCs has attracted considerable attention in the global science and technology field, with the self-renewal and multidirectional differentiation potential for diabetes, obesity treatment, bone repair, nerve repair, myocardial repair, and so on. Epigenetics plays an important role in the regulation of mesenchymal stem cell differentiation, which has become a research hotspot in the medical field. This review focuses on the role of lysine acetylation modification on the determination of MSC differentiation direction. During this progress, the recruitment of lysine acetyltransferases (KATs) and lysine deacetylases (KDACs) is the crux of transcriptional mechanisms in the dynamic regulation of key genes controlling MSC multidirectional differentiation.

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The LIM protein Ajuba promotes adipogenesis by enhancing PPARγ and p300/CBP interaction

Cited by 28 publications

References 45 publications

Amentoflavone protects against high fat-induced metabolic dysfunction: Possible role of the regulation of adipogenic differentiation

Amentoflavone protects against high fat-induced metabolic dysfunction: Possible role of the regulation of adipogenic differentiation

The LIM domain protein nTRIP6 acts as a co-repressor for the transcription factor MEF2C in myoblasts

Concise Review: The Regulatory Mechanism of Lysine Acetylation in Mesenchymal Stem Cell Differentiation

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