Dice J F, Terlecky S R
Department of Physiology, Tufts University School of Medicine, Boston, MA 02111.
Crit Rev Ther Drug Carrier Syst. 1990;7(3):211-33.
We review evidence for a pathway by which specific cytosolic proteins are targeted to lysosomes for degradation in cultured cells in response to serum withdrawal. This pathway is also activated by starvation in several rat tissues. The enhanced degradation is specific for a class of intracellular proteins containing peptide sequences related to residues 7 to 11 of ribonuclease A (RNase A). The amino acid sequence of this pentapeptide is lysine-phenylalanine-glutamate-arginine-glutamine, or, in single letter amino acid abbreviations, KFERQ. A heat shock protein of 73 kDa binds to such peptide regions in proteins and somehow mediates their transfer to lysosomes for degradation. The recent reconstitution of this lysosomal pathway of proteolysis in vitro should permit detailed mechanistic analysis of how proteins are directed to and translocated across lysosomal membranes.
我们综述了关于一条途径的证据，在培养细胞中，特定的胞质蛋白可通过该途径在血清撤除后靶向溶酶体进行降解。在几种大鼠组织中，饥饿也会激活这条途径。增强的降解作用针对的是一类细胞内蛋白质，这类蛋白质含有与核糖核酸酶A（RNase A）第7至11位残基相关的肽序列。这个五肽的氨基酸序列是赖氨酸-苯丙氨酸-谷氨酸-精氨酸-谷氨酰胺，或者用单字母氨基酸缩写表示为KFERQ。一种73 kDa的热休克蛋白会与蛋白质中的此类肽区域结合，并以某种方式介导它们转移至溶酶体进行降解。最近在体外重建了这条溶酶体蛋白水解途径，这应该能对蛋白质如何被导向溶酶体膜并穿过溶酶体膜进行详细的机制分析。
