Topic
Transcription Factor CHOP
About: Transcription Factor CHOP is a research topic. Over the lifetime, 443 publications have been published within this topic receiving 46408 citations.
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TL;DR: It is reported that P0S63del is misfolded and Schwann cells mount a consequential canonical unfolded protein response (UPR), including expression of the transcription factor CHOP, previously associated with apoptosis in ER-stressed cells and indicates that signaling through the CHOP arm of the UPR provokes demyelination in inherited neuropathy.
242 citations
TL;DR: Findings demonstrate that proteins within the C/EBP family directly modulate transcription from the PPAR gamma 2 promoter.
233 citations
TL;DR: The data suggest that CHOP functions as an inducible inhibitor of adipocytic differentiation in response to metabolic stress by interfering with the accumulation of adipogenic C/EBP isoforms.
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.
233 citations
TL;DR: The role of amino acid limitation in regulating the expression of CHOP, a CCAAT/enhancer binding protein (C/EBP)-related gene, is examined and it is found that decreasing amino acid concentration by itself can induce CHOP expression independently of a cellular stress due to protein synthesis inhibition.
225 citations
TL;DR: Data reveal an unexpected and novel prosur‐vival role of CerS6/C16‐ceramide involved in the protection against ER‐stress‐induced apoptosis and induction of HNSCC tumor growth.
Abstract: Emerging results suggest that ceramides with different fatty acid chain lengths might play distinct functions in the regulation of tumor growth and therapy. Here we report that de novo-generated C(18)- and C(16)-ceramides by ceramide synthases 1 and 6 (CerS1 and CerS6) play opposing proapoptotic and prosurvival roles, respectively, in human head and neck squamous cell carcinomas (HNSCCs). Unexpectedly, knockdown of CerS6/C(16)-ceramide using small interfering RNA induced endoplasmic reticulum (ER)-stress-mediated apoptosis. Reconstitution of C(16)-ceramide generation by induced expression of wild-type CerS6, but not its catalytically inactive mutant, protected cells from cell death induced by knockdown of CerS6. Moreover, using molecular tools coupled with analysis of sphingolipid metabolism showed that generation of C(16)-ceramide, and not dihydro-C(16)-ceramide, by induced expression of CerS6 rescued cells from ER stress and apoptosis. Mechanistically, regulation of ER-stress-induced apoptosis by CerS6/C(16)-ceramide was linked to the activation of a specific arm, ATF6/CHOP, of the unfolded protein response pathway. Notably, while expression of CerS1/C(18)-ceramide inhibited HNSCC xenograft growth, CerS6/C(16)-ceramide significantly protected ER stress, leading to enhanced tumor development and growth in vivo, consistent with their pro- and antiapoptotic roles, respectively. Thus, these data reveal an unexpected and novel prosurvival role of CerS6/C(16)-ceramide involved in the protection against ER-stress-induced apoptosis and induction of HNSCC tumor growth.
224 citations