Defect in serine 46 phosphorylation of p53 contributes to acquisition of p53 resistance in oral squamous cell carcinoma cells

HIPK2-induced p53Ser46 phosphorylation activates the KILLER/DR5-mediated caspase-8 extrinsic apoptotic pathway

“…Thus, it has been shown that p53Ser46 phosphorylation is associated with transcriptional activation of proapoptotic mitochondrial p53AIP1 gene, involving the intrinsic apoptotic pathway. 8,9 In agreement with these data, it has been recently shown that defect in Ser46 phosphorylation contributes to the acquisition of the p53 resistance in an oral squamous cell carcinoma cell line, 10 while a mutant active form of p53, p53-46F, induces apoptosis more effectively than wild-type p53, 11 strengthening the role for this p53 post-translational modification in selective transcription of apoptotic target genes. Starting from these findings, we wanted to investigate whether HIPK2/p53 complex could induce the activation of extrinsic/death receptor pathway.…”

Vinculin negatively regulates transcription of MT1-MMP through MEK/ERK pathway

“…Recent studies have demonstrated that MT1-MMP protects cancer cells from apoptosis induced by collagen gel culture [21]. HSC-4 cells used here express mutant form of p53-R248Q [22] and lack the expression of PTEN (Fig. 1).…”

Restoration of tumor suppressor p53 by differentially regulating pro- and anti-p53 networks in HPV-18-infected cervical cancer cells

“…DNA damage signals are known to induce phosphorylation of serine-15 culminating in increased stability and nuclear localization of p53 (Frank et al, 2006;Amano et al, 2009). On the other hand, phospho-serine-46 is required for transcriptional regulation of many p53-dependent genes involved in cell cycle arrest and apoptosis (Ichwan et al, 2006). Interestingly, phosphorylation at serine-15 in some cases is a prerequisite for different protein kinases to induce transcriptionally active p53 (Ichwan et al, 2006).…”

“…On the other hand, phospho-serine-46 is required for transcriptional regulation of many p53-dependent genes involved in cell cycle arrest and apoptosis (Ichwan et al, 2006). Interestingly, phosphorylation at serine-15 in some cases is a prerequisite for different protein kinases to induce transcriptionally active p53 (Ichwan et al, 2006). As observed in our study, celecoxib-activated ATM, blocking which significantly abrogated apoptosis and p53 phosphorylation at both serine-15 and serine-46, sparing p38MAPK which still remained active.…”