Dissociation of Kar2p/BiP from an ER sensory molecule, Ire1p, triggers the unfolded protein response in yeast
Dissociation of Kar2p/BiP from an ER sensory molecule, Ire1p, triggers the unfolded protein response in yeast
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DOI：
10.1006/bbrc.2000.3987
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发表时间：
2000-12-20
影响因子：
3.1
通讯作者：
Kohno, K
中科院分区：
文献类型：
--
作者：
Okamura, K;Kimata, Y;Kohno, K
未折叠蛋白反应（unfolded protein response，UPR）是由内质网（endoplasmic reticulum，ER）应激诱导的一种信号转导途径，在真核生物中起着维持细胞膜稳态的作用。各种ER应激导致ER中未折叠蛋白的积累，这由跨膜蛋白激酶/核糖核酸酶Ire 1 p感测，所述跨膜蛋白激酶/核糖核酸酶Ire 1 p将信号从ER传递到酿酒酵母中的细胞核。在这里，我们报告酵母ER伴侣Kar 2 p/BiP（ER中发现的HSP 70家族的成员）通过与Ire 1 p的相互作用直接调节UPR。在没有ER应激的情况下，Kar 2 p结合Ire 1 p的内腔结构域并使Ire 1 p保持在无活性的非磷酸化状态。当细胞暴露于ER应激时，Kar 2 p从Ire 1 p释放，导致Ire 1 p的激活和信号转导到细胞核。随后，KAR 2 mRNA被诱导，Kar 2 p以时间依赖性的方式在ER中积累，使系统恢复到基础状态。这种负性自身调节类似于哺乳动物细胞溶质分子伴侣Hsp 70通过其与热休克因子1的相互作用的调节。(C)北京大学出版社.
The unfolded protein response (UPR) is a signal transduction pathway induced by a variety of endoplasmic reticulum (ER) stresses and functions to maintain homeostasis of the cellular membrane in eukaryotes. Various ER stresses result in the accumulation of unfolded proteins in the ER, which is sensed by the transmembrane protein kinase/ribonuclease Ire1p that transmits a signal from the ER to the nucleus in Saccharomyces cerevisiae. Here we report that the yeast ER chaperone Kar2p/BiP, a member of the HSP70 family found in the ER, directly regulates the UPR by the interaction with Ire1p. In the absence of ER stress, Kar2p binds the lumenal domain of Ire1p and keeps Ire1p in an inactive unphosphorylated state. Upon exposure of cells to ER stresses, Kar2p is released from Ire1p, resulting in activation of Ire1p and signal transduction to the nucleus. Subsequently, KAR2 mRNA is induced and Kar2p accumulates in the ER in a time-dependent manner, restoring the system to the basal state. This negative autoregulation is similar to the regulation of mammalian cytosolic chaperone Hsp70 via its interaction with heat shock factor 1. (C) 2000 Academic Press.