A role for the phosphatidylinositol 3-kinase--protein kinase C zeta--Sp1 pathway in the 1,25-dihydroxyvitamin D3 induction of the 25-hydroxyvitamin D3 24-hydroxylase gene in human kidney cells

Cellular Signalling
P P DwivediCharles S T Hii

Abstract

The molecular mechanisms that underlie non-genomic induction of the 25-hydroxyvitamin D3 24-hydroxylase (CYP24) gene promoter by the steroid hormone, 1,25-Dihydroxyvitamin D3 (1,25D), are poorly understood. Although we have previously identified a functional inverted GC-box in the early promoter at -113/-105 bp, it is not known whether this site is important for 1,25D induction of the promoter. Using transfected human embryonic kidney (HEK) 293T cells, we now report the functional characterisation of the GC-box and that 1,25D induction of the promoter requires PI3-kinase, PKCzeta and Sp1 but not Sp3. The data show that 1,25D rapidly stimulates PI3-kinase activity which is required for the activation of PKCzeta and the phosphorylation of Sp1. The effects of the PI3-kinase inhibitor, LY294002, and a dominant negative PKCzeta mutant on 1,25D induction of wild-type and a GC-box mutated CYP24 promoter constructs are consistent with the Sp1 site being the target of both kinases. However, these kinases are not required for basal expression of the CYP24 promoter. The data establish a novel non-genomic mechanism which couples 1,25D to the induction of CYP24 gene transcription via the PI3-kinase--PKCzeta--Sp1 pathway acting through the G...Continue Reading

References

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Citations

Mar 15, 2012·Clinical Biochemistry·Paul H AndersonHoward A Morris
Mar 8, 2016·Nutrients·Charles S Hii, Antonio Ferrante
Sep 17, 2013·Molecular Nutrition & Food Research·Chunxiao GuoAdrian F Gombart
May 9, 2013·International Journal of Molecular Sciences·Li PangShulan Zhang
Aug 1, 2015·Nutrients·Noor H A SuainiLeonard C Harrison
Jul 19, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ahmed El-Sharkawy, Ahmed Malki
Dec 30, 2016·Reviews in Endocrine & Metabolic Disorders·Harjit Pal BhattoaPawel Pludowski

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