Analysis of the regulation of simple epithelia-specific intermediate filament proteins, Keratin 8/18

点击翻译按钮获取中文摘要

Keratin 8 and 18 (K8/18) are the major components of intermediate filament (IF) proteins of simple or single-layered epithelia. In this study, we screened a yeast two-hybrid library, using K8 or K18 as a bait in order to search for unidentified K8/18-associated proteins. We identified human Mrj and human TNF receptor 1-associated death domain protein (TRADD), as K18-interacting proteins. Mrj is a protein that belongs to a DnaJ/Hsp40 family, and we found that Mrj might be involved in the regulation of the K8/18 filament organization as a K18-specific co-chaperone to work together with Hsp/c70. TFIADD is an indispensable adaptor molecule for TNF receptor 1 signaling, and we demonstrated that K1 8 might sequester TRADD to attenuate interactions of TRADD with activated TNF receptor 1 and moderate TNF-induced apoptosis in simple epithelial cells. We have also identified (a) nucleoporin p62, a constituent of nuclear pore complexes, (b) ATF5/ATFx, a transcriptional factor, (c) an unidentified protein showng similarity with trichohyalin and plectin, as K8-binding proteins, and have been studying the physiological meanings of these interactions.