OBJECTIVES The human stress protein BiP (immunoglobulin binding protein) has been implicated in the pathogenesis of rheumatoid arthritis (RA) since BiP was found to stimulate synovial T-cell proliferation and anti-BiP antibodies are present in the serum of RA patients. The aim of this study was the development of a rapid and reproducible enzyme-linked immunosorbent assay (ELISA) to determine th...

The target of rapamycin (TOR) kinase integrates nutritional and stress signals to coordinately control cell growth in all eukaryotes. TOR associates with highly conserved proteins to constitute two distinct signaling complexes termed TORC1 and TORC2. Inactivation of TORC1 by rapamycin negatively regulates protein synthesis in most eukaryotes. Here, we report that down-regulation of TOR signalin...

VIP36 is an intracellular lectin that cycles between the endoplasmic reticulum (ER) and the Golgi apparatus, and is thought to act as a cargo receptor in the transport and sorting of glycoproteins. Here we sought to identify the proteins that interact with VIP36 during the quality control of secretory proteins. VIP36 was crosslinked and immunoprecipitated from HEK293 cells that expressed Myc-ta...

Co-chaperones regulate chaperone activities and are likely to impact a protein-folding environment as much as the chaperone itself. As co-chaperones are expressed substoichiometrically, the ability of co-chaperones to encounter a chaperone is crucial for chaperone activity. ERdj3, an abundant soluble endoplasmic reticulum (ER) co-chaperone of the Hsp70 BiP, stimulates the ATPase activity of BiP...

DnaK/Hsp70 chaperones form oligomers of poorly understood structure and functional significance. Site-specific proteolysis and crosslinking were used to probe the architecture of oligomers formed by the endoplasmic reticulum (ER) Hsp70, BiP. These were found to consist of adjacent protomers engaging the interdomain linker of one molecule in the substrate binding site of another, attenuating the...

BiP is the predominant DnaK/Hsp70-type chaperone protein in the ER. It is required for folding and assembling newly synthesized ER client proteins, yet having too much BiP inhibits folding. In this issue, Chambers et al. (2012. J. Cell Biol. doi:10.1083/jcb.201202005) report that ADP ribosylation of BiP provides a reversible switch that fine tunes BiP activity according to need.

Men court-mandated to attend a batterer's intervention program (BIP) were evaluated to determine whether pre-BIP readiness to change and the presence of partner violence subtypes predicted BIP completion, criminal recidivism, and postadjudication partner violence 6 months post-BIP. Of the 199 subject sample, 40% did not complete BIP. Four readiness-to-change clusters were found, with most men (...

Endoplasmic reticulum (ER) stress-induced activation of ATF6, an ER membrane-bound transcription factor, requires a dissociation step from its inhibitory regulator, BiP. It has been generally postulated that dissociation of the BiP-ATF6 complex is a result of the competitive binding of misfolded proteins generated during ER stress. Here we present evidence against this model and for an active r...

Previous studies have demonstrated that overexpression of GRP78/BiP, an endoplasmic reticulum (ER)-resident molecular chaperone, in mammalian cells inhibits the secretion of specific coagulation factors. However, the effects of GRP78/BiP on activation of the coagulation cascade leading to thrombin generation are not known. In this study, we examined whether GRP78/BiP overexpression mediates cel...

The aim of the present study was to identify main risk factors and treatment needs batterer intervention program (BIP) participants with alcohol drug abuse problems (ADAPs), beyond issues strictly related their substance abuse, taking into account four sets variables: sociodemographic (i.e., age, educational level, income, employment, immigrant status); personality disorders psychological adjus...