Role and regulation of the ER chaperone BiP

BiP, an HSP70 molecular chaperone located in the lumen of the endoplasmic r eticulum (ER), binds newly-synthesized proteins as they are translocated in to the ER and maintains them in a state competent for subsequent folding an d oligomerization. BiP is also an essential component of the translocation machinery, as well as playing a role in retrograde transport across the ER membrane of aberrant proteins destined for degradation by the proteasome. B iP is an abundant protein under all growth conditions, but its synthesis is markedly induced under conditions that lead to the accumulation of unfolde d polypeptides in the ER. This attribute provides a marker for disease stat es that result from misfolding of secretory and transmembrane proteins.