Chop is a ubiquitously expressed mammalian gene encoding a small nuclear protein related to the CCAAT/enhancer-binding protein (C/EBP) family of transcription factors. CHOP protein plays an important role in various cellular processes such as growth, differentiation and programmed cell death. CHOP expression is strongly increased in response to a large variety of stresses including perturbation of the endoplasmic reticulum function, DNA damage and nutrient deprivation. Multiple mechanisms including transcriptional and post-transcriptional controls are involved in the regulation of CHOP expression. We show here that the 5'UTR of the Chop transcript plays an important role in controlling the synthesis of CHOP protein. In particular, the 5'UTR contains a conserved uORF which encodes a 31 amino acid peptide that inhibits the expression of the downstream ORF. Mutational analysis of the 5' leader region and peptide coding sequences suggests that the peptide itself inhibits expression of the downstream ORF. Such results suggest a role for uORF in limiting ribosomal access to downstream initiation sites. With respect to the importance of CHOP protein in the regulation of cellular functions, the mechanisms that regulate its basal level are of considerable interest.

译文

Chop是一种普遍表达的哺乳动物基因,编码与CCAAT/增强子结合蛋白 (C/EBP) 转录因子家族相关的小核蛋白。CHOP蛋白在各种细胞过程中起着重要作用,例如生长,分化和程序性细胞死亡。CHOP表达强烈增加,以应对各种压力,包括内质网功能的扰动,DNA损伤和营养剥夺。包括转录和转录后控制在内的多种机制参与了CHOP表达的调节。我们在这里表明,Chop转录本的5'UTR在控制CHOP蛋白的合成中起着重要作用。特别是,5'UTR包含一个保守的uORF,该uORF编码31个氨基酸的肽,该肽抑制下游ORF的表达。对5' 前导区域和肽编码序列的突变分析表明,肽本身会抑制下游ORF的表达。这些结果表明uORF在限制核糖体进入下游起始位点上的作用。关于CHOP蛋白在调节细胞功能中的重要性,调节其基础水平的机制引起了人们的极大兴趣。

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