26S蛋白酶体对核因子-κB p50的共翻译生物合成

Cotranslational biogenesis of NF-kappaB p50 by the 26S proteasome.

作者信息

Lin L, DeMartino G N, Greene W C

机构信息

Gladstone Institute of Virology and Immunology, Department of Microbiology and Immunology, University of California, San Francisco 94141, USA.

出版信息

Cell. 1998 Mar 20;92(6):819-28. doi: 10.1016/s0092-8674(00)81409-9.

DOI:10.1016/s0092-8674(00)81409-9

PMID:9529257

Abstract

The NFkappaB1 gene encodes two functionally distinct proteins termed p50 and p105. p50 corresponds to the N terminus of p105 and with p65 (RelA) forms the prototypical NF-kappaB transcription factor complex. In contrast, p105 functions as a Rel-specific inhibitor (IKB) and has been proposed to be the precursor of p50. Our studies now demonstrate that p50 is generated by a unique cotranslational processing event involving the 26S proteasome, whereas cotranslational folding of sequences near the C terminus of p50 abrogates proteasome processing and leads to p105 production. These results indicate that p105 is not the precursor of p50 and reveal a novel mechanism of gene regulation that ensures the balanced production and independent function of the p50 and p105 proteins.

摘要

NFkappaB1基因编码两种功能不同的蛋白质，分别称为p50和p105。p50对应于p105的N末端，并与p65（RelA）形成典型的NF-κB转录因子复合物。相比之下，p105作为Rel特异性抑制剂（IKB）发挥作用，并被认为是p50的前体。我们现在的研究表明，p50是由涉及26S蛋白酶体的独特共翻译加工事件产生的，而p50 C末端附近序列的共翻译折叠会消除蛋白酶体加工并导致p105的产生。这些结果表明p105不是p50的前体，并揭示了一种新的基因调控机制，该机制确保了p50和p105蛋白的平衡产生和独立功能。