Year: 2016
Type: article
Abstract: Although previous studies indicate that loss of p53-mediated cell cycle arrest, apoptosis, and senescence does not completely abrogate its tumor suppression function, it is unclear how the remaining activities of p53 are regulated. Here, we have identified an acetylation site at lysine K98 in mouse p53 (or K101 for human p53). Whereas the loss of K98 acetylation (p53 K98R ) alone has very modest effects on p53-mediated transactivation, simultaneous mutations at all four acetylation sites (p53 4KR : K98R+ 3KR[K117R+K161R+K162R]) completely abolish its ability to regulate metabolic targets, such as TIGAR and SLC7A11. Notably, in contrast to p53 3KR , p53 4KR is severely defective in suppressing tumor growth in mouse xenograft models. Moreover, p53 4KR is still capable of inducing the p53-Mdm2 feedback loop, but p53-dependent ferroptotic responses are markedly abrogated. Together, these data indicate the critical role of p53 acetylation in ferroptotic responses and its remaining tumor suppression activity.
Source: Cell Reports
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,620
Awards: Regulation of Mdmx stability and subcellular localization by ubiquitination, Regulation of SLC7A11 by p53 in cancer metabolism, Regulation of p53 acetylation and deacetylation in tumorigenesis., Systems-wide analysis of histone lysine 2-hydroxyisobutyrylation pathway, HAUSP inhibitors in p53-wild type and p53-mutant tumors, Mechanisms of novel cancer targets in ARF-mediated tumor suppression, Biochemistry of lysine crotonylation pathway, Role of p53-mediated unconventional functions in tumor suppression
OpenAlex ID: W2529409645