cardioprotective effects of T3, little is known about the intracellular regulation of its action. Intracellular regulation of nuclear receptors by posttranslational modification by ubiquitin is well known and involves two distinct mechanisms: 1) targeted
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Kristine M Wadosky, Jessica M Berthiaume, Wei Tang, Makhosi Zungu, Michael A Portman, A Martin Gerdes, and Monte S Willis
H K Kinyamu, J Chen, and T K Archer
Introduction Overview of the ubiquitin–proteasome pathway Proteins exist in a dynamic state in the cell, with multiple pathways leading to their degradation ( Glickman & Ciechanover 2002 ). The best
Sachie Nakamichi, Yoko Senga, Hiroshi Inoue, Aki Emi, Yasushi Matsuki, Eijiro Watanabe, Ryuji Hiramatsu, Wataru Ogawa, and Masato Kasuga
Rnf128 ) is a transmembrane RING finger-type E3 ubiquitin ligase. The abundance of GRAIL mRNA is increased in T-lymphocytes in response to the induction of anergy ( Anandasabapathy et al . 2003 ), and the encoded protein plays an important role in the
LK Beitel, YA Elhaji, R Lumbroso, SS Wing, V Panet-Raymond, B Gottlieb, L Pinsky, and MA Trifiro
The androgen receptor (AR) N-terminal domain plays a critical role in androgen-responsive gene regulation. A novel AR N-terminal-interacting protein (ARNIP) was isolated using the yeast two-hybrid system and its interaction with amino acids 11-172 of the normal or corresponding region of the polyglutamine-expanded human AR confirmed by glutathione S-transferase pulldown assays. ARNIP cDNAs cloned from NSC-34 (mouse neuroblastoma/spinal cord) or PC-3 (human prostate adenocarcinoma) mRNA encoded highly homologous 30 kDa (261 amino acids) cysteine-rich proteins with a RING-H2 (C3H2C3 zinc finger) domain; this motif is highly conserved in predicted ARNIP-homologous proteins from several other species. Expression of the approximately 1.7 kb ARNIP mRNA was detected in various tissues by Northern blotting, but was highest in mouse testes, kidney and several neuronal cell lines. In addition, the human ARNIP protein was found to be encoded by nine exons spanning 32 kb on chromosome 4q21. In COS-1 cells, coexpression of ARNIP and AR did not affect AR ligand-binding kinetics, nor did ARNIP act as a coactivator or corepressor in transactivation assays. However, AR N-terminal:C-terminal interaction was reduced in the presence of ARNIP. Intriguingly, ARNIP, and in particular its RING-H2 domain, functioned as a ubiquitin-protein ligase in vitro in the presence of a specific ubiquitin-conjugating enzyme, Ubc4-1. Mutation of a single cysteine residue in the ARNIP RING-H2 domain (Cys145Ala) abolished this E3 ubiquitin ligase activity. Fluorescent protein tagging studies revealed that AR-ARNIP interaction was hormone-independent in COS-1 cells, and suggest that colocalization of both AR and ARNIP to the nucleus upon androgen addition may allow ARNIP to play a role in nuclear processes. Thus, identification of a novel AR-interacting protein with ubiquitin ligase activity will stimulate further investigation into the role of ubiquitination and the ubiquitin-proteasome system in AR-mediated cellular functions.
Kyle T Helzer, Christopher Hooper, Shigeki Miyamoto, and Elaine T Alarid
( Le Romancer et al . 2011 ). Importantly, ERα and other NRs are targets of ubiquitylation, a PTM that couples receptor protein turnover and transcriptional function at multiple levels of the receptor signaling pathway. NR degradation by the ubiquitin
Péter Egri and Balázs Gereben
proteolysis is driven by the ubiquitin–proteasome system (UPS) and represents a crucial regulatory mechanism of cell function ( Hershko & Ciechanover 1998 ). Targeting proteins into the proteasome for degradation is one of the most heavily studied phenomena
Katherine A Robinson, Jonathan W Brock, and Maria G Buse
appears to involve phosphorylation of PI3 kinase, leading to activation of the ubiquitin/proteasome pathway. Materials and methods 3T3-L1 fibroblasts and adipocytes were cultured and differentiated in high (25 mM) glucose and preincubated in low (5 mM) and
Yabing Mi, Wangsheng Wang, Jiangwen Lu, Chuyue Zhang, Yawei Wang, Hao Ying, and Kang Sun
proteasome pathway inhibitors MG132 (10 nM; Selleck, Houston, TX, USA) and bortezomib (50 nM; Selleck) or a ubiquitin-activating Enzyme E1 inhibitor PYR-41 (5 µM; Selleck). The involvement of lysosome pathway was further examined with siRNA-mediated knock
Wei-Ling Fang, Si-Yi Lai, Wei-An Lai, Ming-Ting Lee, Ching-Fong Liao, Ferng-Chun Ke, and Jiuan-Jiuan Hwang
that a Cx43-interacting protein, ubiquitin-ligase Nedd4, is involved in the regulation of internalization and degradation of Cx43 gap junction ( Leykauf et al . 2006 , Mollerup et al . 2011 ). Accordingly, we were interested to understand the role of
Xianglan Sun, Ling Gao, Hung-Yu Chien, Wan-Chun Li, and Jiajun Zhao
), contain a ubiquitin-associated domain located next to the C-terminal of their catalytic domains ( Bright et al . 2009 ), which is required for LKB1 phosphorylation and activation ( Jaleel et al . 2006 ). Homology search analysis of the ARK5 amino acid
