Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The phosphorylation of histone H3 is known to play a role in regulation of transcription as well as preparation of chromosomes for mitosis. Various signaling cascades induce H3 phosphorylation, particularly at genes activated by these pathways. In this study, we show that signaling can also have the opposite effect. Activators of cAMP signaling induce a rapid and potent loss of H3 phosphorylation. This effect is not mediated through a cAMP metabolite since a membrane-permeable form of AMP had no effect on H3 phosphorylation and a phosphodiesterase-resistant cAMP analog efficiently reduced it. cAMP is also the likely regulator of H3 phosphorylation under physiological conditions since only supra-pharmacological doses of cGMP induce the loss of H3 phosphorylation. The loss of phosphorylation is specific for histone H3 since we do not observe drastic losses in total phosphorylation of other histones. In addition, other H3 modifications are unaffected with the exception of lysine 9 methylation, which is elevated. Analysis of cell growth and cell cycle shows that cAMP signaling inhibits cell growth and arrests cells at both G1 and G2/M. Similar effects of cAMP signaling on H3 phosphorylation are observed in a variety of mammary adenocarcinoma-derived cell lines. In syngeneic human breast-derived cell lines, one diploid and non-transformed, the other derived from a ductal carcinoma, the loss of H3 phosphorylation is significantly more sensitive to cAMP concentration in the transformed cell line.
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PMID:cAMP signaling induces rapid loss of histone H3 phosphorylation in mammary adenocarcinoma-derived cell lines. 1795 Feb 76

Calmodulin (CaM) is a ubiquitous, calcium-binding protein that regulates several important aspects of cellular metabolism. A number of enzymes such as phosphodiesterase (PDE-1) are stimulated by CaM. In previous studies, our results showed that artemisinin (ART) is a potent inhibitor of CaM and PDE-1 activity. In this study, the effects of dihydroartemisinin (DHA) that is a semisynthesized agent from the ART on CaM structure were investigated. The result showed that DHA increased fluorescence emission of CaM in higher amounts compared with the ART. Also, the effect of DHA on CaM-dependent PDE-1 activity was studied. Kinetic analysis of the DHA-CaM interaction showed that this agent competitively inhibited the activation of PDE-1 without affecting Vmax. Km values of PDE-1 in the presence of ART and DHA were 10 and 15 microM, respectively; DHA increased Km value in higher amounts compared with the ART. The Ki constants for ART and DHA were 10 microM and 7.3 microM, respectively. As a conclusion, CaM and CaM-dependent PDE-1 were inhibited by DHA more than ART. The data indicated that DHA could stimulate the delayed type hypersensitivity (DTH) against sheep blood cells in Balb/c mice and reduced the tumor growth in vivo against invasive ductal carcinoma in Balb/c mice.
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PMID:Dihydroartemisinin can inhibit calmodulin, calmodulin-dependent phosphodiesterase activity and stimulate cellular immune responses. 1990 May 84