The MYC protein is a transcription factor with oncogenic potential controlling fundamental cellular processes such as cell proliferation, metabolism, differentiation, and apoptosis. The MYC gene is a major cancer driver, and elevated MYC protein levels are a hallmark of most human cancers. We have previously shown that the brain acid-soluble protein 1 gene (BASP1) is specifically downregulated by the v-myc oncogene and that ectopic BASP1 expression inhibits v-myc-induced cell transformation. The 11-amino acid effector domain of the BASP1 protein interacts with the calcium sensor calmodulin (CaM) and is mainly responsible for this inhibitory function. We also reported recently that CaM interacts with all MYC variant proteins and that ectopic CaM increases the transactivation and transformation potential of the v-Myc protein. Here, we show that the presence of excess BASP1 or of a synthetic BASP1 effector domain peptide leads to displacement of v-Myc from CaM. The protein stability of v-Myc is decreased in cells co-expressing v-Myc and BASP1, which may account for the inhibition of v-Myc. Furthermore, suppression of v-Myc-triggered transcriptional activation and cell transformation is compensated by ectopic CaM, suggesting that BASP1-mediated withdrawal of CaM from v-Myc is a crucial event in the inhibition. In view of the tumor-suppressive role of BASP1 which was recently also reported for human cancer, small compounds or peptides based on the BASP1 effector domain could be used in drug development strategies aimed at tumors with high MYC expression.

中文翻译：

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脑酸可溶蛋白1（BASP1）干扰MYC的致癌能力及其与钙调蛋白的结合。

MYC蛋白是具有致癌潜力的转录因子，可控制基本的细胞过程，例如细胞增殖，代谢，分化和凋亡。MYC基因是主要的癌症驱动因素，而MYC蛋白水平升高是大多数人类癌症的标志。我们以前已经表明，脑酸可溶性蛋白1基因（BASP1）被v-myc癌基因特异性下调，而异位BASP1表达抑制v-myc诱导的细胞转化。BASP1蛋白的11个氨基酸的效应域与钙传感器钙调蛋白（CaM）相互作用，并主要负责这种抑制功能。最近我们还报道了CaM与所有MYC变异蛋白相互作用，而异位CaM增加了v-Myc蛋白的反式激活和转化潜能。这里，我们表明，过量的BASP1或合成的BASP1效应域肽的存在导致v-Myc从CaM置换。在共表达v-Myc和BASP1的细胞中，v-Myc的蛋白质稳定性降低，这可能解释了v-Myc的抑制作用。此外，异位CaM补偿了对v-Myc触发的转录激活和细胞转化的抑制，这表明BASP1介导的CaM从v-Myc退出是抑制的关键事件。鉴于最近还报道了BASP1对人类癌症的抑制作用，基于BASP1效应子结构域的小化合物或肽可用于针对具有高MYC表达的肿瘤的药物开发策略。在共表达v-Myc和BASP1的细胞中，v-Myc的蛋白质稳定性降低，这可能解释了v-Myc的抑制作用。此外，异位CaM补偿了对v-Myc触发的转录激活和细胞转化的抑制，这表明BASP1介导的CaM从v-Myc退出是抑制的关键事件。鉴于最近还报道了BASP1对人类癌症的抑制作用，基于BASP1效应子结构域的小化合物或肽可用于针对具有高MYC表达的肿瘤的药物开发策略。在共表达v-Myc和BASP1的细胞中，v-Myc的蛋白质稳定性降低，这可能解释了v-Myc的抑制作用。此外，异位CaM补偿了对v-Myc触发的转录激活和细胞转化的抑制，这表明BASP1介导的CaM从v-Myc退出是抑制的关键事件。鉴于最近还报道了BASP1对人类癌症的抑制作用，基于BASP1效应子结构域的小化合物或肽可用于针对具有高MYC表达的肿瘤的药物开发策略。提示BASP1介导的CaM从v-Myc退出是抑制的关键事件。鉴于最近还报道了BASP1对人类癌症的抑制作用，基于BASP1效应子结构域的小化合物或肽可用于针对具有高MYC表达的肿瘤的药物开发策略。提示BASP1介导的CaM从v-Myc退出是抑制的关键事件。鉴于最近还报道了BASP1对人类癌症的抑制作用，基于BASP1效应子结构域的小化合物或肽可用于针对具有高MYC表达的肿瘤的药物开发策略。