期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1991
卷号：88
期号：4
页码：1565-1569
DOI：10.1073/pnas.88.4.1565
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：The endoplasmic reticulum of mammalian cells contains a heat shock protein of approximately 70 kDa (hsp70) termed binding protein BiP that is thought to promote the folding and subunit assembly of newly synthesized proteins. To study BiP function, we placed the BiP-encoding gene from Saccharomyces cerevisiae under the control of a regulated promoter and examined the effects of BiP depletion. Reduction of BiP protein to about 15% of normal levels led to a profound reduction in secretion of alpha factor and invertase. At the same time, unglycosylated precursors of these proteins accumulated intracellularly. The predominant form of the invertase precursor had undergone signal sequence cleavage but accumulated as a soluble species in the cytosol. In contrast, the alpha-factor precursor was exclusively in the signal-uncleaved form. It sedimented with microsomal membranes and was exposed at the cytoplasmic face in a protease-resistant form. These findings suggest that, in yeast, BiP function is required for translocation of soluble proteins into the endoplasmic reticulum at a stage beyond the initial nascent chain-membrane association.
