Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.7 (DNA polymerase)
 17,007 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To understand the effects of the immunosuppressant cyclosporin A (CsA) on Ca2+-mediated intracellular signalling pathways in human peripheral blood mononuclear cells (PBMCs), we investigated its effects on the activity profiles of mitogen-activated protein kinase (MAPK) cascades. PBMCs, or subpopulations thereof, were simultaneously stimulated with a phorbol ester and the calcium ionophore ionomycin, in the presence or absence of therapeutic concentrations of CsA. In these primary human cells, CsA significantly inhibited PMA/ionomycin-mediated and ionomycin-mediated activation of the MAPK kinase MKK6, as well as its downstream kinases SAPK2a (p38alpha) and MAPKAP-K2. PMA/ionomycin treatment also mediated activation of SAPK1 (JNKs) which was inhibited by CsA. Treatment with ionomycin alone also resulted in CsA-sensitive activation of SAPK1. With regard to transcription factors targeted by the Ca2+-induced MAPK signalling network, we found CsA to inhibit the ionomycin-mediated phosphorylation of ATF2 at Thr71. We identified the heterodimeric transcription factor ATF2/CREB as constitutively binding to the essential cAMP response element (CRE) site within the Ca2+-regulated DNA polymerase beta promoter and contributing to the activation of this promoter. Our data implicate ATF2 phosphorylation status as a nuclear sensor within PBMCs that monitors converging intracellular Ca2+-signalling pathways.
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PMID:Ca2+-induced p38/SAPK signalling inhibited by the immunosuppressant cyclosporin A in human peripheral blood mononuclear cells. 1051 4

The solitary cAMP response element (CRE)1 in the human DNA polymerase beta (beta-pol) core promoter plays a key role in both basal expression and the DNA-alkylating agent response of the promoter. To further understand the role of the CRE in the regulation of this promoter, we searched for novel CRE-binding proteins by using a 32P-labeled beta-pol CRE oligodeoxynucleotide and a human cDNA expression library constructed in phage lambda. A total of fourteen phage clones were isolated, corresponding to various members of the CRE-binding protein family. One of these clones, termed ATF2 deletion (ATF2d), encodes a novel ATF2 isoform and was chosen for further characterization in this study. Relative to ATF2 mRNA, this clone contains an internal 97-nt deletion and a unique 3' region. The 97-nt deletion causes a frame shift, resulting in a ATF2-like polypeptide of approximately 60 kDa. ATF2d retains the bZIP domain of ATF2, lacks the N-terminal zinc-finger region, and includes novel characteristics in its N- and C-terminal regions.
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PMID:Cloning and characterization of a novel member of the human ATF/CREB family: ATF2 deletion, a potential regulator of the human DNA polymerase beta promoter. 1290 47