Abstract
CARF (Collaborator of ARF) was discovered as an ARF-interacting protein that activated ARF-p53-p21WAF1 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.
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Abbreviations
- CARF:
-
Collaborator of ARF
- DDR:
-
DNA damage response
- UPR:
-
Unfolded protein response
- ROS:
-
Reactive oxygen species
- CTA:
-
Cell transformation assay
- IC:
-
Inhibitory concentration
- ER:
-
Endoplasmic reticulum
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The present study is supported by the grants from the Department of Biotechnology (Government of India) and AIST (Japan).
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RSK, RW, and SCK designed the study, interpreted the results, and wrote the manuscript. RSK, AC, AO, and SG performed the experiments and coordinated in result compilation. CTC helped in interpretation of results and manuscript writing.
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Kalra, R.S., Chaudhary, A., Omar, A. et al. Stress-induced changes in CARF expression determine cell fate to death, survival, or malignant transformation. Cell Stress and Chaperones 25, 481–494 (2020). https://doi.org/10.1007/s12192-020-01088-y
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DOI: https://doi.org/10.1007/s12192-020-01088-y