To examine how binding of BiP (a molecular chaperone of the hsp70 family that resides in the endoplasmic reticulum) influences the conformational maturation of thyroglobulin (Tg, the precursor for thyroid hormone synthesis), we have developed a system of recombinant Tg stably expressed in wild-type Chinese hamster ovary (CHO) cells and CHO-B cells genetically manipulated for selectively increas...

Cyclopentenone prostaglandins (PGs) are transported into cells and stimulate the expression of various stress genes, such as that coding for BiP (an ER luminal protein). To reveal the site of action of the PGs for the induction of stress-gene expression, we introduced a fluorescent probe, pyrene, into two types of PG analogue, GIF0010 (a cyclopentenone type) and GIF0037 (a cyclopentanone type) ...

Ribosomes synthesizing secretory and membrane proteins are bound to the endoplasmic reticulum (ER) membrane and attach to ribosome-associated membrane proteins such as the Sec61 complex, which forms the protein-conducting channel in the membrane. The ER membrane-resident Hsp40 protein ERj1 was characterized as being able to recruit BiP to ribosomes in solution and to regulate protein synthesis ...

We take a fresh look at the expressivity of BIP, a recent influential formal component model developed by J. Sifakis et al. We introduce a process calculus, called CAB, that models composite components as the combination of a glue (using BIP terminology) and subcomponents, and that constitutes a conservative extension of BIP with more dynamic forms of glues. We study the Turing completeness of ...

We reconstituted prepro-alpha-factor translocation and signal peptide processing using a yeast microsomal detergent soluble fraction formed into vesicles with soybean phospholipids. Reconstituted translocation required ATP, and was deficient when sec63 and kar2 (BiP) mutant cells were used as a source of membranes. Normal translocation was observed with vesicles reconstituted from a mixture of ...

Proteins of the Hsp70 family of ATPases, such as BiP, function together with J proteins to bind polypeptides in numerous cellular processes. Using a solid phase binding assay, we demonstrate that a conserved segment of the J proteins, the J domain, catalytically activates BiP molecules to bind peptides in its immediate vicinity. The J domain interacts with the ATP form of BiP and stimulates hyd...

Bax is a pro-apoptotic member of the Bcl-2 family of proteins, and plays a central role in mitochondria-dependent apoptosis. Several lines of evidence have implied that Bax is involved in both epithelial apoptosis and fibroblast proliferation in idiopathic pulmonary fibrosis; however, the mechanisms remain unknown. Bax-inhibiting peptide V5 (BIP-V5) exhibits membrane permeability and inhibits t...

In prostate cancer, oxidative stress and the subsequent Nrf2 activation promote the survival of cancer cells and acquired chemoresistance. Nrf2 links prostate cancer to endoplasmic reticulum stress, an event that triggers the unfolded protein response, aiming to restore cellular homeostasis as well as an adaptive survival mechanism. Glucose-regulated protein of 78 kD /immunoglobulin heavy chain...

This paper studies a general methodology and an associated tool for translating AADL (Architecture Analysis and Design Language) and annex behavior specification into the BIP (Behavior Interaction Priority) language. This allows simulation of systems specified in AADL and application to these systems of formal verification techniques developed for BIP, e.g. deadlock detection. We present a conc...

Verification and validation techniques have become popular in software and hardware development. They increase the confidence and potentially provide rich feedback on errors. However, with increasing complexity verification and validation techniques are more likely to contain errors themselves. In this paper we address the problem of guaranteeing the correctness of validation work with respect ...