Protein L-isoaspartyl methyltransferase regulates p53 activity

Jae Cheol Lee, Sung Ung Kang, Yeji Jeon, Jong Woo Park, Jueng Soo You, Shin Won Ha, Narkhyun Bae, Gert Lubec, So Hee Kwon, Ju Seog Lee, Eun Jung Cho, Jeung Whan Han

Research output: Contribution to journalArticlepeer-review

43 Citations (Scopus)


Protein methylation plays important roles in most, if not all, cellular processes. Lysine and arginine methyltransferases are known to regulate the function of histones and non-histone proteins through the methylation of specific sites. However, the role of the carboxyl-methyltransferase protein L-isoaspartyl methyltransferase (PIMT) in the regulation of protein functions is relatively less understood. Here we show that PIMT negatively regulates the tumour suppressor protein p53 by reducing p53 protein levels, thereby suppressing the p53-mediated transcription of target genes. In addition, PIMT depletion upregulates the proapoptotic and checkpoint activation functions of p53. Moreover, PIMT destabilizes p53 by enhancing the p53-HDM2 interaction. These PIMT effects on p53 stability and activity are attributed to the PIMT-mediated methylation of p53 at isoaspartate residues 29 and 30. Our study provides new insight into the molecular mechanisms by which PIMT suppresses the p53 activity through carboxyl methylation, and suggests a therapeutic target for cancers.

Original languageEnglish
Article number927
JournalNature communications
Publication statusPublished - 2012

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)


Dive into the research topics of 'Protein L-isoaspartyl methyltransferase regulates p53 activity'. Together they form a unique fingerprint.

Cite this