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Frame-shifted APOBEC3A encodes two alternative pro-apoptotic proteins that target the mitochondrial network

Abstract : 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 pro-apoptotic proteins, A3A cytidine deaminases that target the genome and A3Alt proteins that target mitochondria.
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https://hal-pasteur.archives-ouvertes.fr/pasteur-03333737
Contributor : Vincent Caval <>
Submitted on : Friday, September 3, 2021 - 11:04:52 AM
Last modification on : Monday, September 6, 2021 - 11:54:33 AM

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Vincent Caval, Rodolphe Suspène, Pierre Khalfi, Julien Gaillard, Grégory Caignard, et al.. Frame-shifted APOBEC3A encodes two alternative pro-apoptotic proteins that target the mitochondrial network. Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2021, 297 (3), pp.101081. ⟨10.1016/j.jbc.2021.101081⟩. ⟨pasteur-03333737⟩

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