RRC ID 46583
Author Darom A, Bening-Abu-Shach U, Broday L.
Title RNF-121 is an endoplasmic reticulum-membrane E3 ubiquitin ligase involved in the regulation of beta-integrin.
Journal Mol Biol Cell
Abstract We report on the characterization of RNF-121, an evolutionarily conserved E3 ligase RING finger protein that is expressed in the endoplasmic reticulum (ER) of various cells and tissues in Caenorhabditis elegans. Inactivation of RNF-121 induced an elevation in BiP expression and increased the sensitivity of worms to ER stress. Genetic analysis placed RNF-121 downstream of the unfolded protein response (UPR) regulator protein kinase-like endoplasmic reticulum kinase (PERK). We identify PAT-3::GFP, the beta subunit of the heterodimeric integrin receptors, as an RNF-121 substrate; whereas induction of RNF-121 expression reduced the level of PAT-3::GFP in the gonad distal tip cells, inhibition of RNF-121 led to the accumulation of stably bound PAT-3::GFP inclusions. Correspondingly, overexpression of RNF-121 during early stages of gonad development led to aberrations in germline development and gonad migration that overlap with those observed after PAT-3 inactivation. The formation of these gonad abnormalities required functional ER-associated degradation (ERAD) machinery. Our findings identify RNF-121 as an ER-anchored ubiquitin ligase that plays a specific role in the ERAD pathway by linking it to the regulation of the cell adhesion integrin receptors.
Volume 21(11)
Pages 1788-98
Published 2010-6-1
DOI 10.1091/mbc.e09-09-0774
PII E09-09-0774
PMID 20357004
PMC PMC2877638
MeSH Animals Animals, Genetically Modified Caenorhabditis elegans / anatomy & histology Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Cell Cycle Proteins / genetics Cell Cycle Proteins / metabolism Endoplasmic Reticulum / enzymology* Gonads / abnormalities Gonads / metabolism Heat-Shock Proteins / genetics Heat-Shock Proteins / metabolism Integrin beta Chains / genetics Integrin beta Chains / metabolism* MAP Kinase Kinase 1 / genetics MAP Kinase Kinase 1 / metabolism RING Finger Domains* RNA Interference Recombinant Fusion Proteins / genetics Recombinant Fusion Proteins / metabolism Signal Transduction / physiology Stress, Physiological Ubiquitin-Protein Ligases / genetics Ubiquitin-Protein Ligases / metabolism* eIF-2 Kinase / genetics eIF-2 Kinase / metabolism
IF 3.791
Times Cited 27
C.elegans tm794