Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.1.99.3 (PRE)
 1,923 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The nontransformed steroid receptors contain several non-steroid binding proteins, such as hsp90, hsp70, and p59. Recently, we and others have shown that p59 (FKBP59) is an immunophilin which binds two potent immunosuppressants, FK506 and rapamycin. This raises the possibility that FK506 or rapamycin may modify the function of steroid receptors. To develop this line of inquiry, we chose a yeast model system in which the human progesterone receptor form B (hPR-B) was cotransformed with a reporter gene. The reporter contains two copies of a progesterone response element/glucocorticoid response element (PRE/GRE) upstream of the CYC1 promoter which are linked to the lacZ gene of Escherichia coli. We found that FK506 potentiated the ability of progesterone in activating transcription. To gain insight into the mechanism of FK506's regulation of PR action, we questioned whether calcineurin is involved, because it has been shown that FK506 is a specific inhibitor of calcineurin, a Ca(2+)- and calmodulin-regulated phosphatase, through the formation of an FKBP12-FK506-calcineurin-calmodulin complex. We found that 15-O-desmethyl-FK520, an FK506 analogue which is an excellent ligand of FKBP12, but a poor inhibitor of calcineurin, failed to induce the same effect as FK506. We also found that calmidazolium, a calmodulin antagonist, mimicked FK506's action. Furthermore, immunoblot analysis showed that both FK506 and calmidazolium potentiated the effect of progesterone in decreasing the mobility of hPR-B upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). This suggests that FK506 and calmidazolium may cooperate with progesterone in increasing the level of hPR-B phosphorylation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Potentiation of progesterone receptor-mediated transcription by the immunosuppressant FK506. 752 Dec 10

Photolyase/blue-light photoreceptor family of proteins includes cyclobutane pyrimidine dimer photolyase, (6-4) photolyase and blue-light photoreceptors that were recently discovered in Arabidopsis thaliana, Sinapis alba and Chlamydomonas reinhardtii. Recently, we identified two human genes, hCRY1 and hCRY2, belonging to this family. The proteins encoded by these genes have no DNA repair activity and therefore were hypothesized to function in human blue-light response reactions. To identify downstream targets for these putative blue-light photoreceptors we searched for interacting proteins by the yeast two-hybrid method. We found that the tetratricopeptide repeat protein 1, Tpr1, and the protein serine/threonine phosphatase 5 (PP5) that contains the TPR motif specifically interacted with hCRY2. The effect of the hCRY2-PP5 interaction on the protein phosphatase activity was investigated. We found that hCRY2, but not the highly homologous (6-4) photolyase, inhibits the phosphatase activity of PP5. This inhibition may be on the pathway of blue-light signal transduction reaction in humans.
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PMID:Human blue-light photoreceptor hCRY2 specifically interacts with protein serine/threonine phosphatase 5 and modulates its activity. 938 98

The cyclobutane pyrimidine dimer (CPD) is a major type of DNA damage induced by ultraviolet B (UVB) radiation. CPD photolyase, which absorbs blue/UVA light as an energy source to monomerize dimers, is a crucial factor for determining the sensitivity of rice (Oryza sativa) to UVB radiation. Here, we purified native class II CPD photolyase from rice leaves. As the final purification step, CPD photolyase was bound to CPD-containing DNA conjugated to magnetic beads and then released by blue-light irradiation. The final purified fraction contained 54- and 56-kD proteins, whereas rice CPD photolyase expressed from Escherichia coli was a single 55-kD protein. Western-blot analysis using anti-rice CPD photolyase antiserum suggested that both the 54- and 56-kD proteins were the CPD photolyase. Treatment with protein phosphatase revealed that the 56-kD native rice CPD photolyase was phosphorylated, whereas the E. coli-expressed rice CPD photolyase was not. The purified native rice CPD photolyase also had significantly higher CPD photorepair activity than the E. coli-expressed CPD photolyase. According to the absorption, emission, and excitation spectra, the purified native rice CPD photolyase possesses both a pterin-like chromophore and an FAD chromophore. The binding activity of the native rice CPD photolyase to thymine dimers was higher than that of the E. coli-expressed CPD photolyase. These results suggest that the structure of the native rice CPD photolyase differs significantly from that of the E. coli-expressed rice CPD photolyase, and the structural modification of the native CPD photolyase leads to higher activity in rice.
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PMID:The native cyclobutane pyrimidine dimer photolyase of rice is phosphorylated. 1823 36