G protein-coupled receptor kinase 5 modifies cancer cell resistance to paclitaxel

Molecular and Cellular Biochemistry
Joann LagmanChristopher H So

Abstract

G protein-coupled receptor kinases (GRKs) phosphorylate the activated forms of G protein-coupled receptors (GPCRs), leading to receptor desensitization and internalization. In addition, GRKs can modify the activity of many non-GPCR-signaling pathways as well, controlling other cellular functions beyond that directly associated with a GPCR. In this report, we show that cervical cancer HeLa cells and breast cancer MDA MB 231 cells with reduced GRK5 expression display increased sensitivity to the apoptotic effects of paclitaxel (Taxol). This effect in cancer cells with low GRK5 levels could be because of blunted histone deacetylase 6 (HDAC6) activity that leads to an increase in α-tubulin acetylation levels, which augments paclitaxel sensitivity. We demonstrate that GRK5 and HDAC6 form a signaling complex in cells and in vitro. GRK5 phosphorylates HDAC6 at Ser-21 to promote its deacetylase activity. Therefore, the GRK5-HDAC6 interaction may contribute to paclitaxel resistance in cancer cells.

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Citations

Aug 23, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Filip BorysHanna Fabczak
Mar 7, 2021·International Journal of Molecular Sciences·Federica MarzanoAlessandro Cannavo
Jan 29, 2021·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Vanessa SokChristopher H So

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Methods Mentioned

BETA
MDA
pulldowns
transfection
acetylation
co-immunoprecipitations
pulldown

Software Mentioned

GraphPad Prism
ImageJ

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