Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.3.1.21 (CPT)
 4,580 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The proper folding and assembly of major histocompatibility complex (MHC) class I molecules in the endoplasmic reticulum (ER) is an intricate process involving a number of components. Nascent heavy chains of MHC class I molecules, translocated into the ER membrane, are rapidly glycosylated and bind the transmembrane chaperone calnexin. In humans, after dissociation from calnexin, fully oxidized MHC class I heavy chains associate with beta 2-microglobulin (beta 2m) and the soluble chaperone calreticulin. This complex interacts with another transmembrane protein, tapasin, which is believed to assist in MHC class I folding as well as in mediating the interaction between assembling MHC class I molecules and the transporter associated with antigen processing (TAP). The TAP heterodimer (TAP1-TAP2) introduces the final component of the MHC class I molecule by translocating peptides, predominately generated by the proteasome, from the cytosol into the ER where they can bind dimers of beta 2M and the MHC class I heavy chain. Recently, the thiol oxidoreductase ERp57--also known as GRP58, ERp61, ER60, Q2, HIP-70, and CPT and first misidentified as phospholipase C-alpha--has been shown to bind in conjunction with calnexin or calreticulin to a number of newly synthesized ER glycoproteins when their N-linked glycans are trimmed by glucosidases I and II. It was speculated that ERp57 is a generic component of the glycan-dependent ER quality control system. Here, we show that ERp57 is a component of the MHC class I peptide-loading complex. ERp57 might influence the folding of MHC class I molecules at a critical step in peptide loading.
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PMID:The thiol oxidoreductase ERp57 is a component of the MHC class I peptide-loading complex. 963 23

The proper production of the implantation-related factors, leukemia inhibitory factor (LIF), cyclooxygenase 2 (COX2, PTGS2), and prostaglandin E2 (PGE2) in the uterine glands is essential for embryo implantation and the establishment of endometrial receptivity. It has been shown that cAMP-mediated protein kinase A (PKA) signaling regulates the production of these factors. We have previously reported that exchange protein directly activated by cAMP 2 (EPAC2, RAPGEF4), another cAMP mediator, is involved in the differentiation of endometrial stromal cells through the regulation of the expression of calreticulin (CALR). To address whether EPAC2-CALR signaling is involved in the expression of implantation-related factors, we examined the effect of EPAC2 and CALR knockdown on their expression in cultured human endometrial glandular epithelial EM1 cells, treated with forskolin, an adenylyl cyclase activator, an EPAC-selective cAMP analog (8-(4-chlorophenylthio)-2'-O-methyl cAMP (CPT)), or a PKA-selective cAMP analog (N(6)-phenyl-cAMP (Phe)). In addition, the status of cell senescence was examined. EPAC2 knockdown suppressed the expression of CALR protein and mRNA in EM1 cells. Forskolin- or Phe-, but not CPT-, induced expression of LIF or PTGS2 and secretion of PGE2 was inhibited in EPAC2- or CALR-silenced EM1 cells. In addition, knockdown of EPAC2 or CALR increased senescence-associated beta galactosidase activity and expression of p21 but decreased expression of p53. These findings indicate that expression of CALR regulated by EPAC2 in endometrial glandular epithelial cells is critical for the expression of LIF and PTGS2-mediated production of PGE2 through cAMP signaling. Furthermore, EPAC2 and CALR could play a role in the maintenance of gland function.
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PMID:EPAC2-mediated calreticulin regulates LIF and COX2 expression in human endometrial glandular cells. 2537 61