Scidmore M A, Okamura H H, Rose M D
Department of Molecular Biology, Princeton University, New Jersey 08544-1014.
Mol Biol Cell. 1993 Nov;4(11):1145-59. doi: 10.1091/mbc.4.11.1145.
KAR2 encodes the yeast homologue of mammalian BiP, the endoplasmic reticulum (ER) resident member of the HSP70 family. Kar2p has been shown to be required for the translocation of proteins across the ER membrane as well as nuclear fusion. Sec63, an ER integral membrane protein that shares homology with the Escherichia coli DnaJ protein, is also required for translocation. In this paper we describe several specific genetic interactions between these two proteins, Kar2p and Sec63p. First, temperature-sensitive mutations in KAR2 and SEC63 form synthetic lethal combinations. Second, dominant mutations in KAR2 are allele-specific suppressors for the temperature-sensitive growth and translocation defect of sec63-1. Third, the sec63-1, unlike other translocation defective mutations, results in the induction of KAR2 mRNA levels. Taken together, these genetic interactions suggest that Kar2p and Sec63p interact in vivo in a manner similar to that of the E. coli HSP70, DnaK, and DnaJ. We propose that the interaction between these two proteins is critical to their function in protein translocation.
KAR2编码哺乳动物BiP的酵母同源物，即热休克蛋白70（HSP70）家族的内质网（ER）驻留成员。Kar2p已被证明是蛋白质跨内质网膜转运以及核融合所必需的。Sec63是一种内质网整合膜蛋白，与大肠杆菌DnaJ蛋白具有同源性，也是转运所必需的。在本文中，我们描述了Kar2p和Sec63p这两种蛋白质之间的几种特定遗传相互作用。首先，KAR2和SEC63中的温度敏感突变形成合成致死组合。其次，KAR2中的显性突变是sec63-1温度敏感生长和转运缺陷的等位基因特异性抑制子。第三，与其他转运缺陷突变不同，sec63-1会导致KAR2 mRNA水平的诱导。综上所述，这些遗传相互作用表明Kar2p和Sec63p在体内的相互作用方式类似于大肠杆菌HSP70、DnaK和DnaJ。我们认为这两种蛋白质之间的相互作用对它们在蛋白质转运中的功能至关重要。
