Novel role of pleckstrin homology domain of the Bcr-Abl protein: analysis of protein-protein and protein-lipid interactions

Experimental Cell Research
Daria MiroshnychenkoPontus Aspenström

Abstract

The Bcr-Abl protein is a marker for malignant transformation in chronic myeloid leukemia and in acute lymphoblastic leukemia. There are three Bcr-Abl chimeras known so far, p190, p210 and p230. The only structural difference between the three Bcr-Abl proteins is the presence of DH and PH domains from the Bcr gene in p210 and p230. The Bcr-Abl DH domain is functioning as a guanine nucleotide exchange factor for Rho family of small GTPases. The PH domain confers binding to phosphoinositides but some PH domains have also been found to bind specific target proteins. Here we show that the PH domain from Bcr-Abl binds a number of proteins involved in vital cellular processes. These proteins include PLCvarepsilon, Zizimin1, tubulin and SMC1. The revelation of the role of the Bcr-Abl PH domain in leukemogenesis is likely to provide clues to the molecular mechanisms underlying the phenotypes of Bcr-Abl positive leukemia and could therefore provide tools for the identification of targets for the development of therapeutic treatments.

Citations

Jun 7, 2014·Nature Communications·Julien ViaudFrédérique Gaits-Iacovoni
Feb 12, 2011·BMC Biochemistry·Sun-Ju YiNora Heisterkamp
May 18, 2010·Biochemical Pharmacology·Con SullivanShaoguang Li
Jul 12, 2012·Advances in Biological Regulation·Julien ViaudBernard Payrastre
Nov 19, 2019·Cell Structure and Function·Sayaka KashiwagiYusuke Ohba
Dec 6, 2017·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Kentaro ShimasakiKiyotaka Nishikawa

❮ Previous
Next ❯

Related Concepts

Related Feeds

Bioinformatics in Biomedicine

Bioinformatics in biomedicine incorporates computer science, biology, chemistry, medicine, mathematics and statistics. Discover the latest research on bioinformatics in biomedicine here.

Blood And Marrow Transplantation

The use of hematopoietic stem cell transplantation or blood and marrow transplantation (bmt) is on the increase worldwide. BMT is used to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Here is the latest research on bone and marrow transplantation.