Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P11021 (BiP)
 2,049 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transcription of the gene encoding GRP78/BiP, a calcium-binding molecular chaperone localized in the endoplasmic reticulum, is induced in mammalian cells through gradual depletion of the intracellular calcium stores. The multimeric CCAAT binding factor, CBF/NF-Y, binds to the most proximal CCAAT regulatory element (C1) of the grp78 promoter required for both basal level expression and stress response. Using an in vitro transcription system, we show through factor competition and immunodepletion that the grp78 C1-mediated enhancement of transcription requires primarily CBF. Correlating with the previous observation that CBF binding to the 78C1 site is enhanced by EGTA and EDTA, these divalent cation chelators specifically stimulate 78C1-directed transcription. In contrast, increasing amounts of calcium ions are inhibitory. These results provide evidence that CBF is functionally important in transactivating the grp78 C1 transcriptional activity, and suggest a possible mechanism by which grp78 transcription is stimulated by calcium depletion. We further discovered that in addition to binding CBF, both the 78C1 element and the CBF binding site of the alpha2(I) collagen promoter interact weakly with the multifunctional transcription factor YY1. Our studies show that the binding sites for CBF and YY1 are distinct for the two promoter sites, suggesting that YY1 and other interacting factors could exert differential effects on individual promoters bearing the same CBF site.
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PMID:Calcium-sensitive transcriptional activation of the proximal CCAAT regulatory element of the grp78/BiP promoter by the human nuclear factor CBF/NF-Y. 891 May 50

The unfolded protein response is an evolutionarily conserved mechanism whereby cells respond to stress conditions that target the endoplasmic reticulum (ER). The transcriptional activation of the promoter of GRP78/BiP, a prosurvival ER chaperone, has been used extensively as an indicator of the onset of the UPR. YY1, a constitutively expressed multifunctional transcription factor, activates the Grp78 promoter only under ER stress conditions. Previously, in vivo footprinting analysis revealed that the YY1 binding site of the ER stress response element of the Grp78 promoter exhibits ER stress-induced changes in occupancy. Toward understanding the underlying mechanisms of these unique phenomena, we performed chromatin immunoprecipitation analyses, revealing that YY1 only occupies the Grp78 promoter upon ER stress and is mediated in part by the nuclear form of ATF6. We show that YY1 is an essential coactivator of ATF6 and uncover their specific interactive domains. Using small interfering RNA against YY1 and insertional mutation of the gene encoding ATF6alpha, we provide direct evidence that YY1 and ATF6 are required for optimal stress induction of Grp78. We also discovered enhancement of the ER-stressed induction of the Grp78 promoter through the interaction of YY1 with the arginine methyltransferase PRMT1 and evidence of its action through methylation of the arginine 3 residue on histone H4. Furthermore, we detected ER stress-induced binding of the histone acetyltransferase p300 to the Grp78 promoter and histone H4 acetylation. A model for the ER stress-mediated transcription factor binding and chromatin modifications at the Grp78 promoter leading to its activation is proposed.
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PMID:Endoplasmic reticulum stress induction of the Grp78/BiP promoter: activating mechanisms mediated by YY1 and its interactive chromatin modifiers. 1589 57