Tian Lin, Holmgren Robert A, Matouschek Andreas
Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, 2205 Tech Drive, Evanston, Illinois 60208, USA.
Nat Struct Mol Biol. 2005 Dec;12(12):1045-53. doi: 10.1038/nsmb1018. Epub 2005 Nov 20.
The proteasome degrades some proteins, such as transcription factors Cubitus interruptus (Ci) and NF-kappaB, to generate biologically active protein fragments. Here we have identified and characterized the signals in the substrate proteins that cause this processing. The minimum signal consists of a simple sequence preceding a tightly folded domain in the direction of proteasome movement. The strength of the processing signal depends primarily on the complexity of the simple sequence rather than on amino acid identity, the resistance of the folded domain to unraveling by the proteasome and the spacing between the simple sequence and folded domain. We show that two unrelated transcription factors, Ci and NF-kappaB, use this mechanism to undergo partial degradation by the proteasome in vivo. These findings suggest that the mechanism is conserved evolutionarily and that processing signals may be widespread in regulatory proteins.
蛋白酶体降解一些蛋白质，如转录因子间断翅脉（Ci）和核因子κB（NF-κB），以产生具有生物活性的蛋白质片段。在此，我们已经鉴定并表征了底物蛋白质中导致这种加工的信号。最小信号由蛋白酶体移动方向上紧折叠结构域之前的一个简单序列组成。加工信号的强度主要取决于简单序列的复杂性，而非氨基酸同一性、折叠结构域对蛋白酶体解折叠的抗性以及简单序列与折叠结构域之间的间距。我们表明，两种不相关的转录因子Ci和NF-κB在体内利用这种机制被蛋白酶体进行部分降解。这些发现表明该机制在进化上是保守的，并且加工信号可能在调节蛋白中广泛存在。
