Dice J F
Department of Physiology, Tufts University School of Medicine, Boston, Massachusetts 02111.
FASEB J. 1987 Nov;1(5):349-57. doi: 10.1096/fasebj.1.5.2824267.
Multiple pathways of intracellular protein breakdown operate within cells, and the activities of different pathways can be regulated under different physiological conditions. Recent studies suggest that molecular determinants within proteins target them for different pathways of proteolysis. Proteins that are partially unfolded and have an unblocked amino-terminal amino acid with a bulky side chain appear to be good substrates for cytosolic, ubiquitin-mediated pathways of proteolysis. Certain modifications of internal residues such as oxidation of methionines also increase the susceptibility of certain proteins to ubiquitin-mediated proteolysis. Rapidly degraded normal proteins contain peptide regions rich in proline, glutamate, serine, and threonine (PEST regions). The pathway of degradation for these proteins has not been established, but they may be good substrates for calcium-activated proteases. In addition, a lysosomal pathway of protein degradation is activated when serum is withdrawn from cultured cells and is selective for cytosolic proteins containing peptide regions similar to Lys-Phe-Glu-Arg-Gln (KFERQ). This short review summarizes our current understanding of mechanisms of protein breakdown in eukaryotes and evaluates potential molecular determinants of protein half-lives.
细胞内存在多种蛋白质降解途径，不同途径的活性可在不同生理条件下受到调控。近期研究表明，蛋白质中的分子决定因素会使其靶向不同的蛋白水解途径。部分展开且氨基末端氨基酸未被阻断且侧链较大的蛋白质似乎是胞质中泛素介导的蛋白水解途径的良好底物。内部残基的某些修饰，如甲硫氨酸的氧化，也会增加某些蛋白质对泛素介导的蛋白水解的敏感性。快速降解的正常蛋白质含有富含脯氨酸、谷氨酸、丝氨酸和苏氨酸的肽区域（PEST区域）。这些蛋白质的降解途径尚未明确，但它们可能是钙激活蛋白酶的良好底物。此外，当从培养细胞中去除血清时，会激活溶酶体蛋白降解途径，该途径对含有类似于Lys-Phe-Glu-Arg-Gln（KFERQ）肽区域的胞质蛋白具有选择性。这篇简短的综述总结了我们目前对真核生物中蛋白质降解机制的理解，并评估了蛋白质半衰期的潜在分子决定因素。
