Transcription and Human Biology Laboratory, School of Biotechnology, Jawaharlal Nehru University, New Delhi, Delhi, India.
PLoS One. 2013 Aug 16;8(8):e71016. doi: 10.1371/journal.pone.0071016. eCollection 2013.
p53 and calcium signaling are inter-dependent and are known to show both synergistic and antagonistic effects on each other in the cellular environment. However, no molecular mechanism or cellular pathway is known which shows direct regulation between these important cellular signaling molecules. Here we have shown that in cancer cells treated with anti-neoplastic drug GaQ3, p53, there is an increase in intracellular calcium levels by transcriptional regulation of a novel calcium channel gene TRPC6. p53 directly binds to a 22 bp response element in the TRPC6 gene promoter and increase its mRNA and protein expression. Over-expression of TRPC6 results in calcium-dependent apoptotic death and activation of apoptotic genes in a variety of cancer cells. This research work shows that p53 and its transcriptional activity is critical in regulation of calcium signaling and an increase in the intracellular calcium level might be one of the anti-cancer strategies to induce apoptosis in cancer cells.
p53 和钙信号相互依存，在细胞环境中已知它们之间具有协同和拮抗作用。然而，目前尚不知道有哪种分子机制或细胞途径可以直接调节这些重要的细胞信号分子。在这里，我们已经表明，在用抗癌药物 GaQ3 处理的癌细胞中，p53 通过对新型钙通道基因 TRPC6 的转录调控，导致细胞内钙水平升高。p53 直接结合到 TRPC6 基因启动子中的 22 个碱基对反应元件，增加其 mRNA 和蛋白表达。TRPC6 的过表达导致多种癌细胞中钙依赖性凋亡死亡和凋亡基因的激活。这项研究工作表明，p53 及其转录活性在钙信号的调节中至关重要，增加细胞内钙水平可能是诱导癌细胞凋亡的一种抗癌策略。
