Serine/threonine kinase 31 promotes PDCD5-mediated apoptosis in p53-dependent human colon cancer cells
Serine/threonine kinase 31 promotes PDCD5-mediated apoptosis in p53-dependent human colon cancer cells
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DOI：
10.1002/jcp.27079
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发表时间：
2019-03-01
影响因子：
5.6
通讯作者：
Choi, Kyung-Chul
中科院分区：
文献类型：
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作者：
Kwak, Sungmin;Lee, Seung-Hyun;Choi, Kyung-Chul
尽管程序性细胞死亡5（PDCD 5）是p53介导的促凋亡信号传导中的重要蛋白，但对PDCD 5相关的细胞死亡知之甚少。在这项研究中，我们报告丝氨酸/苏氨酸激酶31（STK 31）与PDCD 5相互作用，维持PDCD 5的稳定性。STK 31过表达显著激活PDCD 5稳定和p53介导的细胞凋亡对依托泊苷（ET）的反应。然而，STK 31敲低并不增强ET处理的细胞凋亡。此外，当STK 31耗尽时，PDCD 5抑制ET对p53信号通路的激活，表明PDCD 5-STK 31网络在p53激活中具有重要作用。重要的是，STK 31通过基因毒性应激通过PDCD 5介导的细胞凋亡的正性调节激活p53信号通路。因此，我们证明STK 31的过表达极大地抑制了肿瘤生长，并增加了HCT 116人结直肠癌细胞的化疗敏感性。综上所述，这些发现表明STK 31-PDCD 5复合物网络调节癌细胞的凋亡，并且STK 31是通过诱导PDCD 5介导的凋亡来抑制结肠癌细胞的肿瘤发生的正性凋亡调节剂，以响应遗传毒性应激。
Although programed cell death 5 (PDCD5) is an important protein in p53-mediated proapoptotic signaling, very little is known about PDCD5-related cell death. In this study, we report that serine/threonine kinase 31 (STK31) interacts with PDCD5, which maintains the stability of PDCD5. STK31 overexpression significantly activated PDCD5 stabilization and p53-mediated apoptosis in response to etoposide (ET). However, STK31 knockdown did not enhance apoptosis by ET treatment. Moreover, when STK31 was depleted, PDCD5 inhibited the activation of the p53 signaling pathway with ET, indicating that the PDCD5-STK31 network has an essential role in p53 activation. Importantly, STK31 activated the p53 signaling pathway by genotoxic stress through positive regulation of PDCD5-mediated apoptosis. We thus demonstrated that overexpression of STK31 greatly inhibited tumorigenic growth and increased the chemosensitivity of HCT116 human colorectal carcinoma cells. Taken together, these findings demonstrate that the STK31-PDCD5 complex network regulates apoptosis of cancer cells, and STK31 is a positive apoptosis regulator that inhibits tumorigenesis of colon cancer cells by inducing PDCD5-mediated apoptosis in response to genotoxic stress.