Non-circadian aspects of BHLHE40 cellular function in cancer.

Q2 Biochemistry, Genetics and Molecular Biology
Zsofia Kiss, Maria Mudryj, Paramita M Ghosh
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Abstract

While many genes specifically act as oncogenes or tumor suppressors, others are tumor promoters or suppressors in a context-dependent manner. Here we will review the basic-helix-loop-helix (BHLH) protein BHLHE40, (also known as BHLHB2, STRA13, DEC1, or SHARP2) which is overexpressed in gastric, breast, and brain tumors; and downregulated in colorectal, esophageal, pancreatic and lung cancer. As a transcription factor, BHLHE40 is expressed in the nucleus, where it binds to target gene promoters containing the E-box hexanucleotide sequence, but can also be expressed in the cytoplasm, where it stabilizes cyclin E, preventing cyclin E-mediated DNA replication and cell cycle progression. In different organs BHLHE40 regulates different targets; hence may have different impacts on tumorigenesis. BHLHE40 promotes PI3K/Akt/mTOR activation in breast cancer, activating tumor progression, but suppresses STAT1 expression in clear cell carcinoma, triggering tumor suppression. Target specificity likely depends on cooperation with other transcription factors. BHLHE40 is activated in lung and esophageal carcinoma by the tumor suppressor p53 inducing senescence and suppressing tumor growth, but is also activated under hypoxic conditions by HIF-1α in gastric cancer and hepatocellular carcinomas, stimulating tumor progression. Thus, BHLHE40 is a multi-functional protein that mediates the promotion or suppression of cancer in a context dependent manner.

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癌症中 BHLHE40 细胞功能的非昼夜节律方面。
虽然许多基因具有特定的致癌基因或抑癌基因的作用,但也有一些基因是肿瘤的促进基因或抑癌基因,其作用方式取决于具体情况。在这里,我们将讨论碱性螺旋环螺旋(BHLH)蛋白 BHLHE40(又称 BHLHB2、STRA13、DEC1 或 SHARP2),它在胃癌、乳腺癌和脑瘤中过度表达,在结直肠癌、食管癌、胰腺癌和肺癌中下调。作为一种转录因子,BHLHE40 在细胞核中表达,与含有 E-box 六核苷酸序列的靶基因启动子结合,但也可在细胞质中表达,稳定细胞周期蛋白 E,阻止细胞周期蛋白 E 介导的 DNA 复制和细胞周期进展。在不同器官中,BHLHE40调节不同的靶标,因此可能对肿瘤发生产生不同的影响。在乳腺癌中,BHLHE40 促进 PI3K/Akt/mTOR 的活化,激活肿瘤进展,但在透明细胞癌中则抑制 STAT1 的表达,引发肿瘤抑制。目标特异性可能取决于与其他转录因子的合作。BHLHE40 在肺癌和食管癌中被肿瘤抑制因子 p53 激活,诱导衰老并抑制肿瘤生长,但在胃癌和肝癌中也会在缺氧条件下被 HIF-1α 激活,刺激肿瘤进展。因此,BHLHE40 是一种多功能蛋白质,它以一种依赖于环境的方式介导癌症的促进或抑制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Genes and Cancer
Genes and Cancer Biochemistry, Genetics and Molecular Biology-Genetics
CiteScore
3.90
自引率
0.00%
发文量
6
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