Transcriptional mechanism of vascular endothelial growth factor-induced expression of protein kinase CβII in chronic lymphocytic leukaemia cells



Al-Sanabra, O, Duckworth, AD, Glenn, MA, Brown, BR, Angelillo, P, Lee, K, Herbert, J, Falciani, , Kalakonda, and Slupsky, JR ORCID: 0000-0002-7410-9004
(2017) Transcriptional mechanism of vascular endothelial growth factor-induced expression of protein kinase CβII in chronic lymphocytic leukaemia cells. Scientific Reports, 7.

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Abstract

A key feature of chronic lymphocytic leukaemia (CLL) cells is overexpressed protein kinase CβII (PKCβII), an S/T kinase important in the pathogenesis of this and other B cell malignancies. The mechanisms contributing to enhanced transcription of the gene coding for PKCβII, PRKCB, in CLL cells remain poorly described, but could be important because of potential insight into how the phenotype of these cells is regulated. Here, we show that SP1 is the major driver of PKCβII expression in CLL cells where enhanced association of this transcription factor with the PRKCB promoter is likely because of the presence of histone marks permissive of gene activation. We also show how vascular endothelial growth factor (VEGF) regulates PRKCB promoter function in CLL cells, stimulating PKCβ gene transcription via increased association of SP1 and decreased association of STAT3. Taken together, these results are the first to demonstrate a clear role for SP1 in the up regulation of PKCβII expression in CLL cells, and the first to link SP1 with the pathogenesis of this and potentially other B cell malignancies where PKCβII is overexpressed.

Item Type: Article
Uncontrolled Keywords: chronic lymphocytic leukaemia, transcriptional regulatory elements
Depositing User: Symplectic Admin
Date Deposited: 27 Feb 2017 09:40
Last Modified: 13 Nov 2020 14:43
DOI: 10.1038/srep43228
Related URLs:
URI: http://livrepository.liverpool.ac.uk/id/eprint/3006076