Ku Haploinsuffiency Causes a Lymphoproliferative Disorder of Immature T-cell Precursors due to Ikaros Malfunction  

Zahide Ozer1,2 , Sanjive Qazi1,3 , Rita Ishkhanian1 , Paul Hasty4 , Hong Ma1 , Fatih M. Uckun1,5,6
1 Systems Immunobiology Laboratory and Developmental Therapeutics Program, Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Los Angeles, CA, 90027;
2 Molecular Oncology Program, Parker Hughes Institute, St. Paul, MN 55113;
3 Department of Biology and Bioinformatics Program, Gustavus Adolphus College, 800 W College Avenue, St. Peter, MN 56082;
4 Department of Molecular Medicine and Institute of Biotechnology, The University of Texas Health Science Center, San Antonio, Texas 78425;
5 Department of Pediatrics, University of Southern California Keck School of Medicine, Los Angeles, CA 90027, USA;
6 Developmental Therapeutics Program, USC Norris Comprehensive Cancer Center, Los Angeles, CA 90089
Author    Correspondence author
International Journal of Molecular Medical Science, 2013, Vol. 3, No. 7   doi: 10.5376/ijmms.2013.03.0007
Received: 16 May, 2013    Accepted: 05 Jun., 2013    Published: 21 Jun., 2013
© 2013 BioPublisher Publishing Platform
This is an open access article published under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract

Ikaros (IK) malfunction has been implicated in the pathogenesis of acute lymphoblastic leukemia (ALL), the most common form of childhood cancer. Therefore, a stringent regulation of IK activity is very important. Here we provide unique genetic and biochemical evidence that the Ku protein components Ku70 and Ku80 act as positive regulators of IK function via formation of IK-Ku70 and IK-Ku80 heterodimers with augmented sequence-specific DNA binding activity. siRNA-mediated depletion of Ku70 or Ku80 reduced the sequence-specific DNA binding activity of IK in EMSA as well as the RT-PCR measured IK target gene expression levels in human cells. The interaction of Ku components with IK likely contributes to the anti-leukemic effects of IK as a tumor suppressor, because Ku70 as well as Ku80 haploinsuffiency in mice caused development of a lymphoproliferative disorder (LPD) involving CD2+CD4+CD8+CD1+IL7R+ thymic T-cell precursors with functional IK deficiency.

Keywords
Immunity; Leukemia; Thymocyte; Lymphocyte; Tumor suppressor
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pornliz suckporn sex videos bbw mom xxx big fucking arabin porn videos teen gril sex video riding hard cock woman hard vagina . Zahide Ozer
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