Molecular Retrovirology Unit, Institut Pasteur, Paris, France.
Molecular Retrovirology Unit, Institut Pasteur, Paris, France.
J Biol Chem. 2021 Sep;297(3):101081. doi: 10.1016/j.jbc.2021.101081. Epub 2021 Aug 14.
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.
人类 APOBEC3A（A3A）胞嘧啶脱氨酶是一种强大的 DNA 突变酶，被认为是肿瘤细胞基因组中体细胞突变的主要来源。然而，在髓样细胞中干扰素刺激后的 APOBEC3A mRNA 水平与 A3A 在蛋白质水平的检测之间存在差异。为了理解这种差异，我们研究了在 APOBEC3A 基因的+1 移码阅读框中编码的两种新型替代“ A3Alt”蛋白的表达。A3Alt-L 及其较短的同工型 A3Alt-S 似乎是靶向线粒体区室的跨膜蛋白，可诱导膜去极化和细胞凋亡。因此，APOBEC3A 基因代表了一个新的例子，其中单个基因编码两种促凋亡蛋白，A3A 胞嘧啶脱氨酶靶向基因组，A3Alt 蛋白靶向线粒体。
