Protein-protein interactions underlie the fundamental processes of every cell. Certain proteins called chaperones specialize in protein folding, maturation, and degradation functions within a cell. BiP is the resident chaperone in the endoplasmic reticulum (ER) of eukaryotic cells. Following adverse cellular conditions, BiP acts as a mediator in returning the cell to homeostasis. Spatial locali...

Cells monitor protein folding by an inbuilt quality-control system in which incorrectly or misfolded folded proteins are tagged for degradation or sent back through a refolding cycle. However, continued accumulation of incorrectly folded proteins triggers the Unfolded Protein Response (UPR), which attempts to re-establish folding homeostasis or commits the cell to apoptosis. In this study, we d...

We have recently shown that an adenovirus carrying REIC/Dkk-3 (Ad-REIC) exhibits a potent tumor-specific cell-killing function for various human cancers. It has also become evident that some human cancers are resistant to Ad-REIC-induced apoptosis. The aim of the present study was to determine the molecular mechanisms of resistance to Ad-REIC. First, we isolated resistant clones from a human pr...

We have studied the possible mechanisms of endoplasmic reticulum (ER) export and retention by using natural residents of the plant ER. Under normal physiological conditions, calreticulin and the lumenal binding protein (BiP) are efficiently retained in the ER. When the ER retention signal is removed, truncated calreticulin is much more rapidly secreted than truncated BiP. Calreticulin carries t...

Reconstituted proteoliposomes derived from solubilized yeast microsomes are able to translocate a secreted yeast mating pheromone precursor (Brodsky, J. L., S. Hamamoto, D. Feldheim, and R. Schekman. 1993. J. Cell Biol. 120:95-107). Reconstituted proteoliposomes prepared from strains with mutations in the SEC63 or KAR2 genes are defective for translocation; the kar2 defect can be overcome by th...

magine inserting a piece of string into an inflated balloon without letting any of the air out. An analogous problem confronts cells in the production of integral membrane-spanning proteins, which must be inserted partway into the ER without letting the ER calcium stores leak into the cytoplasm. On page 261, Haigh and Johnson show that the ER lumenal chaperone protein BiP controls one end of a ...

In extreme learning machines (ELM) the hidden-layer coefficients are randomly set and fixed, while output-layer of neural network computed by a least squares method. The randomly-assigned in ELM known to influence its performance accuracy significantly. this paper we present modified batch intrinsic plasticity (modBIP) method for pre-training random networks. current is devised based on same pr...

n mammalian cells, most membrane proteins are inserted cotranslationally into the ER membrane at sites termed translocons. Although each translocon forms an aqueous pore, the permeability barrier of the membrane is maintained during integration, even when the otherwise tight ribosome– translocon seal is opened to allow the cytoplasmic domain of a nascent protein to enter the cytosol. To identif...