Document Detail

A novel crosstalk between calcium/calmodulin kinases II and IV regulates cell proliferation in myeloid leukemia cells.
MedLine Citation:
PMID:  25446257     Owner:  NLM     Status:  Publisher    
CaMKs link transient increases in intracellular Ca(2+) with biological processes. In myeloid leukemia cells, CaMKII, activated by the bcr-abl oncogene, promotes cell proliferation. Inhibition of CaMKII activity restricts cell proliferation, and correlates with growth arrest and differentiation. The mechanism by which the inhibition of CaMKII results in growth arrest and differentiation in myeloid leukemia cells is still unknown. We report that inhibition of CaMKII activity results in an upregulation of CaMKIV mRNA and protein in leukemia cell lines. Conversely, expression of CaMKIV inhibits autophosphorylation and activation of CaMKII, and elicits G0/G1cell cycle arrest, reducing of cell proliferation. Furthermore, U937 cells expressing CaMKIV show elevated levels of Cdk inhibitors p27(kip1) and p16(ink4a) and reduced levels of cyclins A, B1 and D1. These findings were also confirmed in the K562 leukemic cell line. The relationship between CaMKII and CaMKIV was also observed in primary acute myeloid leukemia (AML) cells, that correlated with their immunophenotype profile. Indeed, immature MO/M1 AML showed increased CaMKIV expression and decreased pCaMKII, whereas highly differentiated M4/M5 AML showed decreased CaMKIV expression and increased pCaMKII. Our data reveal a novel cross-talk between CaMKII and CaMKIV and suggest that CaMKII suppresses the expression of CaMKIV to enable leukemia cell proliferation.
Sara Monaco; Maria Rosaria Rusciano; Angela S Maione; Maria Soprano; Rohini Gomathinayagam; Lance R Todd; Pietro Campiglia; Salvatore Salzano; Lucio Pastore; Eleonora Leggiero; Donald C Wilkerson; Monia Rocco; Carmine Selleri; Guido Iaccarino; Uma Sankar; Maddalena Illario
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-11-15
Journal Detail:
Title:  Cellular signalling     Volume:  -     ISSN:  1873-3913     ISO Abbreviation:  Cell. Signal.     Publication Date:  2014 Nov 
Date Detail:
Created Date:  2014-12-2     Completed Date:  -     Revised Date:  2014-12-3    
Medline Journal Info:
Nlm Unique ID:  8904683     Medline TA:  Cell Signal     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2014. Published by Elsevier Inc.
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