Acetylation halts missense mutant p53 aggregation and rescues tumor suppression in non-small cell lung cancers
TP53 mutations are ubiquitous with tumorigenesis in non-small cell lung cancers (NSCLC). By analyzing the TCGA database, we reported that TP53 missense mutations are correlated with chromosomal instability and tumor mutation burden in NSCLC. The inability of wild-type nor mutant p53 expression can...
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Published in | iScience Vol. 26; no. 7; p. 107003 |
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Main Authors | , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Elsevier Inc
21.07.2023
Elsevier |
Subjects | |
Online Access | Get full text |
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Summary: | TP53 mutations are ubiquitous with tumorigenesis in non-small cell lung cancers (NSCLC). By analyzing the TCGA database, we reported that TP53 missense mutations are correlated with chromosomal instability and tumor mutation burden in NSCLC. The inability of wild-type nor mutant p53 expression can't predict survival in lung cancer cohorts, however, an examination of primary NSCLC tissues found that acetylated p53 did yield an association with improved survival outcomes. Molecularly, we demonstrated that acetylation drove the ubiquitination and degradation of mutant p53 but enhanced stability of wild-type p53. Moreover, acetylation of a missense p53 mutation prevented the gain of oncogenic function observed in typical TP53 mutant-expressing cells and enhanced tumor suppressor functions. Consequently, acetylation inducer targeting of missense mutant p53 may be a viable therapeutic goal for NSCLC treatment and may improve the accuracy of current efforts to utilize p53 mutations in a prognostic manner.
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•Missense mutant p53 is correlated with chromosomal instability in NSCLC•Acetylation enhances mutant p53 ubiquitination and proteasome degradation•Acetylation halts aggregation and rescues tumor suppression of mutant p53 in NSCLC•Acetylated p53, but not p53, is a promising prognosis for patient with NSCLC
Health sciences; Molecular biology; Cancer. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 These authors contributed equally Lead contact |
ISSN: | 2589-0042 2589-0042 |
DOI: | 10.1016/j.isci.2023.107003 |