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PI 3-K signaling pa...
PI 3-K signaling pathway suppresses PMA-induced expression of p21WAF1/ Cip1 in human leukemia cells
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- Pivoriunas, A. (författare)
- Department of Experimental Research, Institute of Experimental and Clinical Medicine, Žygimantu 9, 01102 Vilnius, Lithuania
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- Savickiene, J. (författare)
- Department of Experimental Research, Institute of Experimental and Clinical Medicine, Žygimantu 9, 01102 Vilnius, Lithuania
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- Treigyte, G. (författare)
- Department of Developmental Biology, Institute of Biochemistry, Mokslininku 12, 08662 Vilnius, Lithuania
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- Tunaitis, V. (författare)
- Department of Experimental Research, Institute of Experimental and Clinical Medicine, Žygimantu 9, 01102 Vilnius, Lithuania
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- Navakauskiene, R. (författare)
- Department of Developmental Biology, Institute of Biochemistry, Mokslininku 12, 08662 Vilnius, Lithuania
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- Magnusson, Karl-Eric (författare)
- Linköpings universitet,Hälsouniversitetet,Medicinsk mikrobiologi
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(creator_code:org_t)
- 2007-02-08
- 2007
- Engelska.
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Ingår i: Molecular and Cellular Biochemistry. - : Springer Science and Business Media LLC. - 0300-8177 .- 1573-4919. ; 302:1-2
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Despite the understanding of the importance of phosphoinositide 3-kinase (PI 3-K) signaling pathway in the regulation of cellular proliferation, little is known about its role during phorbol 12-myristate 13-acetate (PMA)-induced differentiation in human leukemia cells. Here, we report a novel finding that PI 3-K inhibition by LY294002 significantly increases p21WAF1/Cip1 expression in PMA-stimulated human leukemia cells NB4 and THP1. LY294002 potentiated expression of p21WAF1/Cip1 via a p53-independent mechanism and did not affect mitogen activated protein kinase (MAPK) activation. Electrophoretic mobility shift (EMSA) experiments revealed that blocking of PI 3-K was associated with increased binding of transcription factor Sp1 to the PMA-responsive sites on the p21WAF1/Cip1 promoter. Pretreatment with rapamycin, an inhibitor of mTOR kinase, decreased the expression of p21WAF1/Cip1 protein in PMA-stimulated NB4 cells. The level of PMA-induced p21WAF1/ Cip1 protein expression was lower in NB4 cells overexpressing wild type protein kinase C ? (PKC ?) compared to those transfected with empty vector or with kinase inactive PKC ?. Sp1 binding to the p21WAF1/Cip1 promoter was completely lost in a wild type PKC ? overexpressing and PMA-stimulated NB4 cells. We demonstrate that PI 3-K signaling pathway suppresses PMA-induced expression of p21WAF1/Cip1 in human leukemia cells, and that this effect is partly mediated by PKC ?. © Springer Science+Business Media, LLC 2007.
Nyckelord
- Differentiation
- Leukemia
- p21WAF1/Cip1
- Phorbol esters
- PI 3-K
- Protein kinase C?
- MEDICINE
- MEDICIN
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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