tailieunhanh - Báo cáo khoa học: Cross-species divergence of the major recognition pathways of ubiquitylated substrates for ubiquitin⁄26S proteasome-mediated proteolysis

The recognition of ubiquitylated substrates is an essential element of ubiqu-itin⁄26S proteasome-mediated proteolysis (UPP), which is mediated directly by the proteasome subunit RPN10 and⁄or RPN13, or indirectly by ubiquitin receptors containing ubiquitin-like and ubiquitin-associated domains. By pull-down and mutagenesis assays, we detected cross-species divergence of the major recognition pathways. | Cross-species divergence of the major recognition pathways of ubiquitylated substrates for ubiquitin 26S proteasome-mediated proteolysis Antony S. Fatimababy1 Ya-Ling Lin1 2 3 Raju Usharani1 Ramalingam Radjacommare1 Hsing-Ting Wang1 Hwang-Long Tsai1 Yenfen Lee1 and Hongyong Fu1 2 3 1 Institute of Plant and MicrobialBiology Academia Sinica Taipei Taiwan 2 Molecular and BiologicalAgriculturalSciences Program Taiwan InternationalGraduate Program NationalChung-Hsing University and Academia Sinica Taipei Taiwan 3 Graduate Institute of Biotechnology and Department of Life Sciences NationalChung-Hsing University Taichung Taiwan Keywords RPN10 RPN13 ubiquitin receptor ubiquitin recognition UBL-UBA factors Correspondence H. Fu Institute of Plant and Microbial Biology Academia Sinica 128 Sec 2 Academia Road Nankang Taipei 115 Taiwan Fax Tel 886 2 2787 1183 E-mail hongyong@ Received 23 October 2009 revised 24 November 2009 accepted 2 December 2009 doi The recognition of ubiquitylated substrates is an essential element of ubiqu-itin proteasome-mediated proteolysis UPP which is mediated directly by the proteasome subunit RPN10 and or RPN13 or indirectly by ubiquitin receptors containing ubiquitin-like and ubiquitin-associated domains. By pull-down and mutagenesis assays we detected cross-species divergence of the major recognition pathways. RPN10 plays a major role in direct recognition in Arabidopsis and yeast based on the strong affinity for the long and K48-linked ubiquitin chains. In contrast both the RPN10 and RPN13 homologs play major roles in humans. For indirect recognition the RAD23 and DSK2 homologs except for the human DSK2 homolog are major receptors. The human RAD23 homolog is targeted to the 26S proteasome by the RPN10 and RPN13 homologs. In comparison Arabidopsis uses UIM1 and UIM3 of RPN10 to bind DSK2 and RAD23 respectively. Yeast uses UIM in RPN10 and LRR in RPN1. Overall multiple proteasome subunits are