Kaneko Chie, Hatakeyama Shigetsugu, Matsumoto Masaki, Yada Masayoshi, Nakayama Keiko, Nakayama Keiichi I
Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka, 812-8582, Japan.
Biochem Biophys Res Commun. 2003 Jan 10;300(2):297-304. doi: 10.1016/s0006-291x(02)02834-6.
UFD2a is a mammalian homolog of Saccharomyces cerevisiae Ufd2, originally described as an E4 ubiquitination factor. UFD2a belongs to the U-box family of ubiquitin ligases (E3s) and likely functions as both an E3 and E4. We have isolated and characterized the mouse gene (Ube4b) for UFD2a. A full-length (approximately 5700 bp) Ube4b cDNA was isolated and the corresponding gene spans >100 kb, comprising 27 exons. Luciferase reporter gene analysis of the 5(') flanking region of Ube4b revealed that nucleotides -1018 to -943 (relative to the translation initiation site) possess promoter activity. This functional sequence contains two putative Sp1 binding sites but not a TATA box. Immunoblot and immunohistochemical analyses revealed that UFD2a is expressed predominantly in the neuronal tissues. We also show that UFD2a interacts with VCP (a AAA-family ATPase) that is thought to mediate protein folding. These data implicate UFD2a in the degradation of neuronal proteins by the ubiquitin-proteasome pathway.
UFD2a是酿酒酵母Ufd2的哺乳动物同源物，最初被描述为一种E4泛素化因子。UFD2a属于泛素连接酶（E3）的U-box家族，可能同时作为E3和E4发挥作用。我们已经分离并鉴定了UFD2a的小鼠基因（Ube4b）。分离出了一个全长（约5700 bp）的Ube4b cDNA，相应的基因跨度超过100 kb，由27个外显子组成。对Ube4b 5′侧翼区域的荧光素酶报告基因分析表明，核苷酸-1018至-943（相对于翻译起始位点）具有启动子活性。这个功能序列包含两个假定的Sp1结合位点，但没有TATA框。免疫印迹和免疫组织化学分析表明，UFD2a主要在神经组织中表达。我们还表明，UFD2a与被认为介导蛋白质折叠的VCP（一种AAA家族ATP酶）相互作用。这些数据表明UFD2a参与泛素-蛋白酶体途径对神经蛋白的降解。
