Protein L-isoaspartyl methyltransferase regulates p53 activity

Collection with item attached
2012
Item details URL
http://open-repository.kisti.re.kr/cube/handle/open_repository/483715.do
DOI
10.1038/ncomms1933
Title
Protein L-isoaspartyl methyltransferase regulates p53 activity
Description
We thank K.Y. Chung, W. S. Choi,, Y.K. Kim, D. W. Seo, J.K. Kang, H.Y.Lee, G. U. Bea and J.S. Kang for comments; D. Reinberg, B. Vogelsteinand H. D. Youn for constructs; E. K. Shin (Woojung BSC, inc.) for dataanalysis of Surface Plasmon Resonance; M.S. Kim and J Zhong (Laboratoryof A. Pandey in Johns Hopkins school of Medicine) for further validationof mass spectrometric results during revising the manuscripts. Thisresearch was supported by Basic Science Research Program through theNational Research Foundation of Korea(NRF) funded by the Ministry ofEducation, Science and Technology (2011-0028282, 2011-0028283,2011-0028284), and by a grant from the National R&D Program for CancerControl, Ministry of Health and Welfare, Republic of Korea (0720140).
abstract
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.
provenance
Made available in Cube on 2018-09-28T14:54:14Z (GMT). No. of bitstreams: 0
language
English
author
Lee, Jae-Cheol
Kang, Sung-Ung
Jeon, Yeji
Park, Jong Woo
You, Jueng-Soo
Ha, Shin-Won
Bae, Narkhyun
Lubec, Gert
Kwon, So Hee
Lee, Ju-Seog
Cho, Eun-Jung
Han, Jeung-Whan
orcid
Lubec, Gert/0000-0002-6333-9461
accessioned
2018-09-28T14:54:14Z
available
2018-09-28T14:54:14Z
issued
2012
citation
NATURE COMMUNICATIONS(3)
issn
2041-1723
uri
http://open-repository.kisti.re.kr/cube/handle/open_repository/483715.do
Funder
교육과학기술부
Funding Program
선도연구센터지원
Project ID
1345177144
Jurisdiction
Rep.of Korea
Project Name
Study of Molecular Mechanism of Epigenome Regulation
rights
openAccess
type
article


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