biostudies-literatureJana SSwedish Cancer Research FoundationMinistry of Human Resource DevelopmentLUA/ALF and the VAJRA Faculty SchemeBarncancerfondenDepartment of Science and Technology, Ministry of Science and Technology, IndiaSwedish Research CouncilIngaBritt och Arne Lundbergs ForskningsstiftelseDepartment of Biotechnology, Ministry of Science and Technology, IndiaRP88256https://www.ebi.ac.uk/biostudies/studies/S-EPMC11415074biostudies-literatureUnknown12In tumors with WT p53, alternate mechanisms of p53 inactivation are reported. Here, we have identified a long noncoding RNA, <i>PITAR</i> (<i>p</i>53 <i>I</i>nactivating <i>T</i>RIM28 <i>A</i>ssociated <i>R</i>NA), as an inhibitor of p53. <i>PITAR</i> is an oncogenic Cancer/testis lncRNA and is highly expressed in glioblastoma (GBM) and glioma stem-like cells (GSC). We establish that <i>TRIM28</i> mRNA, which encodes a p53-specific E3 ubiquitin ligase, is a direct target of <i>PITAR. PITAR</i> interaction with <i>TRIM28</i> RNA stabilized <i>TRIM28</i> mRNA, which resulted in increased TRIM28 protein levels and reduced p53 steady-state levels due to enhanced p53 ubiquitination. DNA damage activated <i>PITAR</i>, in addition to p53, in a p53-independent manner, thus creating an incoherent feLife<i>PITAR</i>, a DNA damage-inducible cancer/testis long noncoding RNA, inactivates p53 by binding and stabilizing <i>TRIM28</i> mRNA.PMC11415074NPDFLU2020-0017(VJR/2021/0000082022–01262STARS211416Pj01H2022-01262PR2021-0026Gupta BMahale SMondal MJha NSomasundaram KPrasasvi KRSantosh VKanduri CChowdhury AJana SKandasami Lfalse<i>PITAR</i>, a DNA damage-inducible cancer/testis long noncoding RNA, inactivates p53 by binding and stabilizing <i>TRIM28</i> mRNA.In tumors with WT p53, alternate mechanisms of p53 inactivation are reported. Here, we have identified a long noncoding RNA, <i>PITAR</i> (<i>p</i>53 <i>I</i>nactivating <i>T</i>RIM28 <i>A</i>ssociated <i>R</i>NA), as an inhibitor of p53. <i>PITAR</i> is an oncogenic Cancer/testis lncRNA and is highly expressed in glioblastoma (GBM) and glioma stem-like cells (GSC). We establish that <i>TRIM28</i> mRNA, which encodes a p53-specific E3 ubiquitin ligase, is a direct target of <i>PITAR. PITAR</i> interaction with <i>TRIM28</i> RNA stabilized <i>TRIM28</i> mRNA, which resulted in increased TRIM28 protein levels and reduced p53 steady-state levels due to enhanced p53 ubiquitination. DNA damage activated <i>PITAR</i>, in addition to p53, in a p53-independent manner, thus creating an incoherent f2024-01-01T00:00:00Z2024 Sep2026-06-01T10:04:12.131Z2025-04-04T08:21:56.763ZS-EPMC114150743930209710.7554/eLife.88256