Otsuki T, Kajigaya S, Ozawa K, Liu J M
Department of Hematology, Jichi Medical School, Yakushiji 3311-1, Minamikawachi, Kawachi, Tochigi, 329-0498, Japan.
Biochem Biophys Res Commun. 1999 Nov 30;265(3):630-5. doi: 10.1006/bbrc.1999.1731.
The function of the Fanconi anemia complementation group A (FANCA) protein remains unclear. To investigate possible protein-protein interactions, we performed yeast two-hybrid screening using a FANCA fragment as bait. Sorting nexin 5 (SNX5), a new member of the human SNX family, was identified as a putative FANCA-binding protein. The interaction between FANCA and SNX5 was confirmed by immunoprecipitation studies. All members of the SNX family have a characteristic amino acid region termed the phox homology (PX) domain. Deletion mutant analysis indicated that the PX domain is not required for binding to FANCA. The SNX proteins are thought to play an important role in receptor trafficking between organelles. We found that overexpression of SNX5 increased FANCA protein levels. Northern blot analysis of SNX5 showed the presence of alternatively spliced transcripts and different expression patterns in various human cancer cell lines and normal tissues. Further studies are needed to elucidate the functional significance of FANCA and SNX5 binding; however, we speculate that FANCA may affect SNX5 traffic with cell surface receptors.
范可尼贫血互补组A（FANCA）蛋白的功能仍不清楚。为了研究可能的蛋白质-蛋白质相互作用，我们以FANCA片段为诱饵进行了酵母双杂交筛选。分选连接蛋白5（SNX5）是人类SNX家族的新成员，被鉴定为一种假定的FANCA结合蛋白。通过免疫沉淀研究证实了FANCA与SNX5之间的相互作用。SNX家族的所有成员都有一个称为磷酯酰肌醇同源（PX）结构域的特征性氨基酸区域。缺失突变分析表明，与FANCA结合不需要PX结构域。SNX蛋白被认为在细胞器之间的受体运输中起重要作用。我们发现SNX5的过表达增加了FANCA蛋白水平。对SNX5的Northern印迹分析显示在各种人类癌细胞系和正常组织中存在可变剪接转录本和不同的表达模式。需要进一步研究以阐明FANCA与SNX5结合的功能意义；然而，我们推测FANCA可能影响SNX5与细胞表面受体的运输。
