Serine/threonine kinase 31 promotes PDCD5‐mediated apoptosis in p53‐dependent human colon cancer cells

Abstract

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.

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“…PDCD5 can be involved in programmed cell death, cell cycle, embryonic development, and immune regulation. The expression rate of PDCD5 deletion was consistent with the positive expression rate of mutant p53 and was decreased in laryngeal squamous cell carcinoma but still unclear in OSCC [ 49 , 50 ]. PDPN was a mucin-type transmembrane glycoprotein, and positive expression of ALDH1/p53/Cyclin D1/PDPN was significantly associated with malignant transformation of OLK [ 51 , 52 ].…”

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“…5b and S8). PDCD5 is an important modulator of the apoptotic pathway required for normal cardiovascular development, and serum PDCD5 has been recently shown to reflect vascular endothelial status, which is significantly correlated with cardiovascular risk [57–59]. Along with a N-terminal methionine excision and a coexisting acetylation, the most probable phosphorylation site was determined to be Ser119 (Fig.…”

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“…The STK31 gene encodes the cell cycle kinase, serine/threonine kinase 31, which is known to promote PDCD5 ‐mediated apoptosis in p53‐dependent human colon cancer cells 34 . It is tempting to speculate as to whether this kinase might also affect phosphorylation of tau and neurofibrillary tangle formation in AD.…”

“…The STK31 gene encodes the cell cycle kinase, serine/threonine kinase 31, which is known to promote PDCD5 ‐mediated apoptosis in p53‐dependent human colon cancer cells. 34 It is tempting to speculate as to whether this kinase might also affect phosphorylation of tau and neurofibrillary tangle formation in AD. However, we note that variants in this gene technically did not fulfill the significant thresholds and are highlighted here as additional results.…”