期刊
JOURNAL OF MOLECULAR CELL BIOLOGY
卷 13, 期 11, 页码 774-785出版社
OXFORD UNIV PRESS
DOI: 10.1093/jmcb/mjab047
关键词
p53; posttranslational modification; reader; PTM code; tumor therapy
类别
资金
- National Key R&D Program of China [2019YFC1005200, 2019YFC1005201]
- National Natural Science Foundation of China [81872311, 82073132]
- Beijing Municipal Natural Science Foundation [7192126]
- Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences [2017-I2M-1-008, 2018-I2M-1-002]
The genome guardian p53 undergoes multiple posttranslational modifications in response to diverse stresses, which coordinate to precisely modulate its diverse properties in different biological contexts. These modifications can recruit 'reader' proteins that specifically recognize them, facilitating the functional readout of p53. Targeting the interplay between posttranslational modifications and reader proteins has become a promising cancer therapeutic strategy.
The genome guardian p53 functions as a transcription factor that senses numerous cellular stresses and orchestrates the corresponding transcriptional events involved in determining various cellular outcomes, including cell cycle arrest, apoptosis, senescence, DNA repair, and metabolic regulation. In response to diverse stresses, p53 undergoes multiple posttranslational modifications (PTMs) that coordinate with intimate interdependencies to precisely modulate its diverse properties in given biological contexts. Notably, PTMs can recruit 'reader' proteins that exclusively recognize specific modifications and facilitate the functional readout of p53. Targeting PTM-reader interplay has been developing into a promising cancer therapeutic strategy. In this review, we summarize the advances in deciphering the 'PTM codes' of p53, focusing particularly on the mechanisms by which the specific reader proteins functionally decipher the information harbored within these PTMs of p53. We also highlight the potential applications of intervention with p53 PTM-reader interactions in cancer therapy and discuss perspectives on the 'PTMomic' study of p53 and other proteins.
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