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© Research
Publication : The Journal of biological chemistry

Frame-shifted APOBEC3A encodes two alternative proapoptotic proteins that target the mitochondrial network.

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in The Journal of biological chemistry - 14 Aug 2021

Caval V, Suspène R, Khalfi P, Gaillard J, Caignard G, Vitour D, Roingeard P, Vartanian JP, Wain-Hobson S

Link to Pubmed [PMID] – 34403699

Link to DOI – 10.1016/j.jbc.2021.101081

J Biol Chem 2021 Sep; 297(3): 101081

The human APOBEC3A (A3A) cytidine deaminase is a powerful DNA mutator enzyme recognized as a major source of somatic mutations in tumor cell genomes. However, there is a discrepancy between APOBEC3A mRNA levels after interferon stimulation in myeloid cells and A3A detection at the protein level. To understand this difference, we investigated the expression of two novel alternative “A3Alt” proteins encoded in the +1-shifted reading frame of the APOBEC3A gene. A3Alt-L and its shorter isoform A3Alt-S appear to be transmembrane proteins targeted to the mitochondrial compartment that induce membrane depolarization and apoptosis. Thus, the APOBEC3A gene represents a new example wherein a single gene encodes two proapoptotic proteins, A3A cytidine deaminases that target the genome and A3Alt proteins that target mitochondria.