cGMP-inhibited 3',5'-cyclic phosphodiesterase 3A

Definition:

Cyclic nucleotide phosphodiesterase with specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes. Has also activity toward cUMP. Independently of its catalytic activity it is part of an E2/17beta-estradiol-induced pro-apoptotic signaling pathway. E2 stabilizes the PDE3A/SLFN12 complex in the cytosol, promoting the dephosphorylation of SLFN12 and activating its pro-apoptotic ribosomal RNA/rRNA ribonuclease activity. This apoptotic pathway might be relevant in tissues with high concentration of E2 and be for instance involved in placenta remodeling.

References:

[1]. Stefan Berrisch, et al. cUMP hydrolysis by PDE3A. Naunyn Schmiedebergs Arch Pharmacol. 2017 Mar;390(3):269-280. [Content Brief]

[2]. Philipp G Maass, et al. PDE3A mutations cause autosomal dominant hypertension with brachydactyly. Nat Genet. 2015 Jun;47(6):647-53. [Content Brief]

[3]. Dianrong Li, et al. Estrogen-Related Hormones Induce Apoptosis by Stabilizing Schlafen-12 Protein Turnover. Mol Cell. 2019 Sep 19;75(6):1103-1116.e9. [Content Brief]

[4]. E Meacci, et al. Molecular cloning and expression of human myocardial cGMP-inhibited cAMP phosphodiesterase. Proc Natl Acad Sci U S A. 1992 May 1;89(9):3721-5. [Content Brief]

[5]. Jie Chen, et al. Structure of PDE3A-SLFN12 complex and structure-based design for a potent apoptosis inducer of tumor cells. Nat Commun. 2021 Oct 27;12(1):6204. [Content Brief]

[6]. P P Cheung, et al. Human platelet cGI-PDE: expression in yeast and localization of the catalytic domain by deletion mutagenesis. Blood. 1996 Aug 15;88(4):1321-9. [Content Brief]

[7]. E Degerman, et al. Single-step affinity purification, partial structure and properties of human platelet cGMP inhibited cAMP phosphodiesterase. Biochim Biophys Acta. 1994 Apr 13;1205(2):189-98. [Content Brief]

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