title: TIE2-mediated tyrosine phosphorylation of H4 regulates DNA damage response by recruiting ABL1.
abstract: DNA repair pathways enable cancer cells to survive DNA damage induced after genotoxic therapies. Tyrosine kinase receptors (TKRs) have been reported as regulators of the DNA repair machinery. TIE2 is a TKR overexpressed in human gliomas at levels that correlate with the degree of increasing malignancy. Following ionizing radiation, TIE2 translocates to the nucleus, conferring cells with an enhanced nonhomologous end-joining mechanism of DNA repair that results in a radioresistant phenotype. Nuclear TIE2 binds to key components of DNA repair and phosphorylates H4 at tyrosine 51, which, in turn, is recognized by the proto-oncogene ABL1, indicating a role for nuclear TIE2 as a sensor for genotoxic stress by action as a histone modifier. H4Y51 constitutes the first tyrosine phosphorylation of core histones recognized by ABL1, defining this histone modification as a direct signal to couple genotoxic stress with the DNA repair machinery.
authors.affiliation: Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Mohammad B
authors.initials: MB
authors.lastname: Hossain
authors.affiliation: Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Rehnuma
authors.initials: R
authors.lastname: Shifat
authors.affiliation: Department of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Science Park, Smithville, TX 78957, USA.
authors.forename: David G
authors.initials: DG
authors.lastname: Johnson
authors.affiliation: Department of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Science Park, Smithville, TX 78957, USA.
authors.forename: Mark T
authors.identifier: 0000-0002-8899-1050
authors.initials: MT
authors.lastname: Bedford
authors.affiliation: Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Konrad R
authors.initials: KR
authors.lastname: Gabrusiewicz
authors.affiliation: Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Nahir
authors.initials: N
authors.lastname: Cortes-Santiago
authors.affiliation: Biomolecular Resource Facility, The University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Xuemei
authors.identifier: 0000-0002-8292-6733
authors.initials: X
authors.lastname: Luo
authors.affiliation: Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Ravesanker
authors.identifier: 0000-0002-1353-8307
authors.initials: R
authors.lastname: Ezhilarasan
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Erik P
authors.initials: EP
authors.lastname: Sulman
authors.affiliation: Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Biochemistry and the Siebens-Drake Medical Research Institute, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario N6A 5C1, Canada.
authors.forename: Shawn S C
authors.initials: SS
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Frederick F
authors.initials: FF
authors.lastname: Lang
authors.affiliation: Department of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Science Park, Smithville, TX 78957, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Tyler
authors.affiliation: Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.; Center for Molecular Medicine and Graduate Institute of Cancer Biology, China Medical University, Taichung 404, Taiwan.
authors.forename: Mien-Chie
authors.initials: MC
authors.lastname: Hung
authors.affiliation: Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.; Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Juan
authors.initials: J
authors.lastname: Fueyo
authors.affiliation: Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.; Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Candelaria
authors.initials: C
authors.lastname: Gomez-Manzano
mesh_terms: D000803:Angiotensin I / Q000378:metabolism; D045744:Cell Line, Tumor; D004249:DNA Damage; D059766:DNA End-Joining Repair; D006657:Histones / Q000378:metabolism*; D006801:Humans; D011485:Protein Binding; D021381:Protein Transport; D000090063:Proto-Oncogene Mas; D016315:Proto-Oncogene Proteins c-abl / Q000378:metabolism*; D011836:Radiation Tolerance / Q000235:genetics; D011839:Radiation, Ionizing; D042787:Receptor, TIE-2 / Q000235:genetics / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*
chemical_list: D006657:Histones; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D014443:Tyrosine; D000803:Angiotensin I; D042787:Receptor, TIE-2; D016315:Proto-Oncogene Proteins c-abl
keywords: ABL1; ANG1; Cell biology; DNA repair; NHEJ; TIE2; oncogenes