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应激诱导蛋白CHOP（Gadd153）对脂肪生成的抑制作用。

Inhibition of adipogenesis by the stress-induced protein CHOP (Gadd153).

作者信息

Batchvarova N, Wang X Z, Ron D

机构信息

Skirball Institute of Biomolecular Medicine, Department of Medicine, New York University Medical Center, NY 10016, USA.

出版信息

EMBO J. 1995 Oct 2;14(19):4654-61. doi: 10.1002/j.1460-2075.1995.tb00147.x.

DOI:10.1002/j.1460-2075.1995.tb00147.x
PMID:7588595
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC394562/
Abstract

Adipocytic conversion of 3T3-L1 cells is dependent on induction of transcription factors from the C/EBP family that activate promoters of adipogenic genes. We find that expression of CHOP, a nuclear protein that dimerizes avidly with C/EBP isoforms alpha and beta and directs the resulting heterodimer away from classic C/EBP-binding sites, markedly inhibits this differentiation process. Surprisingly, the presence of CHOP early in the differentiation process inhibits C/EBP alpha and beta gene expression. Ectopic expression of C/EBP alpha bypasses the inhibitory effect of CHOP on differentiation, providing further evidence that CHOP action is mediated by inhibition of C/EBP alpha gene expression rather than merely inhibiting the encoded protein's DNA-binding activity. A similar pattern of attenuated expression of C/EBP alpha and beta is also observed in cells induced to differentiate in media with low glucose concentration. This stressed culture condition is associated with induction of endogenous CHOP and marked attenuation of the differentiation process. Our data suggest that CHOP functions as an inducible inhibitor of adipocytic differentiation in response to metabolic stress. It does so by interfering with the accumulation of adipogenic C/EBP isoforms.

摘要

3T3-L1细胞的脂肪细胞转化依赖于C/EBP家族转录因子的诱导，这些转录因子可激活脂肪生成基因的启动子。我们发现，CHOP（一种能与C/EBP同工型α和β强烈二聚化并使形成的异二聚体远离经典C/EBP结合位点的核蛋白）的表达显著抑制了这一分化过程。令人惊讶的是，在分化过程早期CHOP的存在会抑制C/EBPα和β基因的表达。C/EBPα的异位表达绕过了CHOP对分化的抑制作用，进一步证明CHOP的作用是通过抑制C/EBPα基因表达介导的，而不仅仅是抑制编码蛋白的DNA结合活性。在低葡萄糖浓度培养基中诱导分化的细胞中也观察到了类似的C/EBPα和β表达减弱模式。这种应激培养条件与内源性CHOP的诱导以及分化过程的显著减弱有关。我们的数据表明，CHOP作为一种对代谢应激有反应的脂肪细胞分化诱导抑制剂发挥作用。它通过干扰脂肪生成C/EBP同工型的积累来实现这一点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2056/394562/08f324b3e4ab/emboj00043-0027-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2056/394562/f4eb2097c160/emboj00043-0023-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2056/394562/f539abc58c96/emboj00043-0024-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2056/394562/4fc6bc276eb9/emboj00043-0025-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2056/394562/92cfcc322b9b/emboj00043-0026-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2056/394562/08f324b3e4ab/emboj00043-0027-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2056/394562/f4eb2097c160/emboj00043-0023-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2056/394562/f539abc58c96/emboj00043-0024-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2056/394562/4fc6bc276eb9/emboj00043-0025-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2056/394562/92cfcc322b9b/emboj00043-0026-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2056/394562/08f324b3e4ab/emboj00043-0027-a.jpg

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2
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Nucleic Acids Res. 1993 Apr 25;21(8):1735-42. doi: 10.1093/nar/21.8.1735.
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Regulation of the C/EBP-related gene gadd153 by glucose deprivation.
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Fusion of the dominant negative transcription regulator CHOP with a novel gene FUS by translocation t(12;16) in malignant liposarcoma.在恶性脂肪肉瘤中，通过12号和16号染色体易位（t(12;16)），显性负性转录调节因子CHOP与新基因FUS发生融合。
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