Combined absence of TRP53 target genes ZMAT3, PUMA and p21 cause a high incidence of cancer in mice.

ABSTRACT: Transcriptional activation of target genes is essential for TP53-mediated tumour suppression, though the roles of the diverse TP53-activated target genes in tumour suppression remains poorly understood. Knockdown of ZMAT3, an RNA-binding zinc-finger protein involved in regulating alternative splicing, in haematopoietic cells by shRNA caused leukaemia only with the concomitant absence of the PUMA and p21, the critical effectors of TRP53-mediated apoptosis and cell cycle arrest respectively. We were interested to further investigate the role of ZMAT3 in tumour suppression beyond the haematopoietic system. Therefore, we generated Zmat3 knockout and compound gene knockout mice, lacking Zmat3 and p21, Zmat3 and Puma or all three genes. Puma^-/-p21^-/-Zmat3^-/- trip

SUBMITTER: Brennan MS 

PROVIDER: S-EPMC10850490 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature