Lin L, Ghosh S
Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, New Haven, Connecticut 06520, USA.
Mol Cell Biol. 1996 May;16(5):2248-54. doi: 10.1128/MCB.16.5.2248.
Transcription factor NF-kappaB is generally considered to be a heterodimer with two subunits, p50 and p65. The p50 subunit has been suggested to be generated from its precursor, p105, via the ubiquitin-proteasome pathway. During processing, the C-terminal portion of p105 is rapidly degraded whereas the N-terminal portion (p50) is left intact. We report here that a 23-amino-acid, glycine-rich region (GRR) in p105 functions as a processing signal for the generation of p50. A GRR-dependent endoproteolytic cleavage downstream of the GRR releases p50 from p105, and this cleavage does not require any specific downstream sequences. p50 can be generated from chimeric precursor p105N-GRR-IkappaBalpha, while the C-terminal portion (IkappaBalpha) can also be recovered, suggesting that p105 processing includes two steps: a GRR-dependent endoproteolytic cleavage and the subsequent degradation of the C-terminal portion. We have also demonstrated that the GRR can direct a similar processing event when it is inserted into a protein unrelated to the NF-kappaB family and that it is therefore an independent signal for processing.
转录因子NF-κB通常被认为是由p50和p65两个亚基组成的异源二聚体。有人提出p50亚基是通过泛素-蛋白酶体途径从其前体p105产生的。在加工过程中，p105的C末端部分迅速降解，而N末端部分（p50）保持完整。我们在此报告，p105中一个23个氨基酸的富含甘氨酸区域（GRR）作为生成p50的加工信号。GRR下游依赖GRR的内蛋白水解切割从p105释放p50，并且这种切割不需要任何特定的下游序列。p50可以从嵌合前体p105N-GRR-IκBα产生，同时C末端部分（IκBα）也可以回收，这表明p105加工包括两个步骤：依赖GRR的内蛋白水解切割和随后C末端部分的降解。我们还证明，当GRR插入与NF-κB家族无关的蛋白质中时，它可以指导类似的加工事件，因此它是一个独立的加工信号。
