Pontin, a new mutant p53-binding protein, promotes gain-of-function of mutant p53

Pontin, a novel interactor of mutant p53 that promotes mutant p53 gain of function

“…9 However, this effect of pontin on wtp53 appears to be cell type specific and is only observed in a subset of cells containing wtp53. 7 Our recent study showed that pontin plays a different role in regulating mutp53; pontin does not regulate mutp53 protein levels, but instead interacts with mutp53 harboring tumor hotspot point missense mutations such as R175H, R248H, and R273H. 7 The pontin-mutp53 interaction is mediated through the mutp53 DNA-binding domain (DBD) and the C-terminus of pontin.…”

“…7 Our recent study showed that pontin plays a different role in regulating mutp53; pontin does not regulate mutp53 protein levels, but instead interacts with mutp53 harboring tumor hotspot point missense mutations such as R175H, R248H, and R273H. 7 The pontin-mutp53 interaction is mediated through the mutp53 DNA-binding domain (DBD) and the C-terminus of pontin. Loss of the pontin-mutp53 interaction abrogates mutp53 GOF in migration, invasion, metastasis, and anchorage-independent cell growth of tumor cells.…”

“…7 Overexpression of pontin is associated with poor survival in cancer patients, especially those containing mutp53 in their tumors. 7 These results highlight the biologic significance of pontin and pontin-dependent mutp53 GOF in tumorigenesis.…”

“…7 Overexpression of pontin is associated with poor survival in cancer patients, especially those containing mutp53 in their tumors. 7 These results highlight the biologic significance of pontin and pontin-dependent mutp53 GOF in tumorigenesis. Pontin has been shown to play a chaperone-like role in the assembly and remodeling of several critical complexes, such as TIP60 complex, INO80 complex, and telomerase complex.…”

“…We recently identified pontin (RUVBL1, also known as TIP49) as a novel mutp53 interacting protein that promotes mutp53 GOF primarily through regulating the transcriptional activity of mutp53 toward a subset of its target genes. 7 Pontin is a highly conserved AAA+ ATPase that is an important component of several protein complexes and is involved in multiple biologic processes, including chromatin remodeling, transcriptional regulation, cell replication, and telomerase activities. 8 Pontin is frequently overexpressed in many human cancers, suggesting a potential role in tumorigenesis.…”