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

Estrogen actions in target organs are normally mediated via activation of nuclear estrogen receptors (ERs). By using mRNA differential display technique, we show, herein, that estradiol-17beta (E(2)) and its catechol metabolite 4-hydroxy-E(2) (4OHE(2)) can modulate uterine gene expression in ERalpha(-/-) mice. Whereas administration of E(2) or 4OHE(2) rapidly up-regulated (4-8-fold) the expression of immunoglobulin heavy chain binding protein (Bip), calpactin I (CalP), calmodulin (CalM), and Sik similar protein (Sik-SP) genes in ovariectomized wild-type or ERalpha(-/-) mice, the expression of secreted frizzled related protein-2 (SFRP-2) gene was down-regulated (4-fold). Bip, CalP, and CalM are calcium-binding proteins and implicated in calcium homeostasis, whereas SFRP-2 is a negative regulator of Wnt signaling. Bip and Sik-SP also possess chaperone-like functions. Administration of ICI-182,780 or cycloheximide failed to influence these estrogenic responses, demonstrating that these effects occur independent of ERalpha, ERbeta, or protein synthesis. In situ hybridization showed differential cell-specific expression of these genes in wild-type and ERalpha(-/-) uteri. Although progesterone can antagonize or synergize estrogen actions, it had minimal effects on these estrogenic responses. Collectively, the results demonstrate that estrogens have a unique ability to influence specific genes in the uterus not involving classical nuclear ERs.
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PMID:Estrogen targets genes involved in protein processing, calcium homeostasis, and Wnt signaling in the mouse uterus independent of estrogen receptor-alpha and -beta. 1089 36

The glucose-regulated protein (GRP78) also referred to as immunoglobulin heavy chain binding protein (Bip) is one of the best characterized endoplasmic reticulum (ER) chaperone proteins, which belongs to the heat-shock protein (HSP) family. GRP78 as a central regulator of ER stress (ERS) plays many important roles in cell survival and apoptosis through controlling the activation of transmembrane ERS sensors: PKR-like ER-associated kinase (PERK), inositol requiring kinase 1 (IRE1), and activating transcription factor 6 (ATF6). Many studies have reported that GRP78 is involved in the physiological and pathological process in female reproduction, including follicular development, corpus luteum (CL), oviduct, uterus, embryo, preimplantation development, implantation/decidualization, and the placenta. The present review summarizes the biological or pathological roles and signaling mechanisms of GRP78 during the reproductive processes. Further study on the functions and mechanisms of GRP78 may provide new insight into mammalian reproduction, which not only enhance the understanding of the physiological roles but also support therapy target against infertility.
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PMID:Roles of Grp78 in Female Mammalian Reproduction. 2838 54