2026-04-17T11:23:25Zhttps://recercat.cat/oai/request
oai:recercat.cat:10230/544112025-12-18T01:19:21Zcom_2072_6col_2072_452952
RECERCAT author Aubrey, Brandon J. author Janic, Ana author Chen, Yunshun author Chang, Catherine author Lieschke, Elizabeth C. author Diepstraten, Sarah T. author Kueh, Andrew J. author Bernardini, Jonathan P. author Dewson, Grant author O’Reilly, Lorraine A. author Whitehead, Lachlan author Voss, Anne K. author Smyth, Gordon K. author Strasser, Andreas author Kelly, Gemma L. 2022-10-17T06:15:19Z2022-10-17T06:15:19Z2018 Mutations in Trp53, prevalent in human cancer, are reported to drive tumorigenesis through dominant-negative effects (DNEs) over wild-type TRP53 function as well as neomorphic gain-of-function (GOF) activity. We show that five TRP53 mutants do not accelerate lymphomagenesis on a TRP53-deficient background but strongly synergize with c-MYC overexpression in a manner that distinguishes the hot spot Trp53 mutations. RNA sequencing revealed that the mutant TRP53 DNE does not globally repress wild-type TRP53 function but disproportionately impacts a subset of wild-type TRP53 target genes. Accordingly, TRP53 mutant proteins impair pathways for DNA repair, proliferation, and metabolism in premalignant cells. This reveals that, in our studies of lymphomagenesis, mutant TRP53 drives tumorigenesis primarily through the DNE, which modulates wild-type TRP53 function in a manner advantageous for neoplastic transformation. © 2018 Aubrey et al. This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/. http://creativecommons.org/licenses/by-nc/4.0/ info:eu-repo/semantics/openAccess TRP53 Dominant-negative effect Tumorigenesis TRP53 target genes Mutant TRP53 exerts a target gene-selective dominant-negative effect to drive tumor development info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion