Open AccessStress-induced changes in CARF expression determine cell fate to death, survival, or malignant transformation
Author(s) -
Rajkumar S. Kalra,
Anupama Chaudhary,
Amr Omar,
Caroline Cheung,
Sukant Garg,
Sunil C. Kaul,
Renu Wadhwa
Publication year - 2020
Publication title -
cell stress and chaperones
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.994
H-Index - 87
eISSN - 1466-1268
pISSN - 1355-8145
DOI - 10.1007/s12192-020-01088-y
Subject(s) - oxidative stress , programmed cell death , microbiology and biotechnology , apoptosis , chemistry , senescence , signal transduction , cell growth , malignant transformation , cell cycle checkpoint , cell , cell fate determination , cell cycle , cancer research , biology , biochemistry , transcription factor , gene
CARF (Collaborator of ARF) was discovered as an ARF-interacting protein that activated ARF-p53-p21 WAF1 signaling involved in cellular response to a variety of stresses, including oxidative, genotoxic, oncogenic, or telomere deprotection stresses, leading to senescence, growth arrest, or apoptosis. Of note, whereas suppression of CARF was lethal, its enrichment was associated with increased proliferation and malignant transformation of cells. These reports have predicted that CARF could serve as a multi-stress marker with a predictive value for cell fates. Here, we recruited various in vitro stress models and examined their effect on CARF expression using human normal fibroblasts. We demonstrate that CARF levels in stress and post-stress conditions could predict the fate of cells towards either death or enhanced proliferation and malignant transformation. We provide extensive molecular evidence that (i) CARF expression changes in response to stress, (ii) it modulates cell death or survival signaling and determines the fate of cells, and (iii) it may serve as a predictive measure of cellular response to stress and an important marker for biosafety.