TIE2-mediated tyrosine phosphorylation of H4 regulates DNA damage response by recruiting ABL1

Mohammad B Hossain; Rehnuma Shifat; David G Johnson; Mark T Bedford; Konrad R Gabrusiewicz; Nahir Cortes-Santiago; Xuemei Luo; Zhimin Lu; Ravesanker Ezhilarasan; Erik P Sulman; Hong Jiang; Shawn S C Li; Frederick F Lang; Jessica Tyler; Mien-Chie Hung; Juan Fueyo; Candelaria Gomez-Manzano

doi:10.1126/sciadv.1501290

TIE2-mediated tyrosine phosphorylation of H4 regulates DNA damage response by recruiting ABL1

Sci Adv. 2016 Apr 1;2(4):e1501290. doi: 10.1126/sciadv.1501290. eCollection 2016 Apr.

Authors

Mohammad B Hossain¹, Rehnuma Shifat¹, David G Johnson², Mark T Bedford², Konrad R Gabrusiewicz¹, Nahir Cortes-Santiago¹, Xuemei Luo³, Zhimin Lu¹, Ravesanker Ezhilarasan⁴, Erik P Sulman⁴, Hong Jiang¹, Shawn S C Li⁵, Frederick F Lang⁶, Jessica Tyler², Mien-Chie Hung⁷, Juan Fueyo⁸, Candelaria Gomez-Manzano⁹

Affiliations

¹ Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
² Department of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Science Park, Smithville, TX 78957, USA.
³ Biomolecular Resource Facility, The University of Texas Medical Branch, Galveston, TX 77555, USA.
⁴ Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
⁵ 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.
⁶ Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
⁷ 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.
⁸ 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.
⁹ 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.

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.

Keywords: ABL1; ANG1; Cell biology; DNA repair; NHEJ; TIE2; oncogenes.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Angiotensin I / metabolism
Cell Line, Tumor
DNA Damage*
DNA End-Joining Repair
Histones / metabolism*
Humans
Protein Binding
Protein Transport
Proto-Oncogene Mas
Proto-Oncogene Proteins c-abl / metabolism*
Radiation Tolerance / genetics
Radiation, Ionizing
Receptor, TIE-2 / genetics
Receptor, TIE-2 / metabolism*
Tyrosine / metabolism*

Substances

Histones
MAS1 protein, human
Proto-Oncogene Mas
Tyrosine
Angiotensin I
Receptor, TIE-2
Proto-Oncogene Proteins c-abl

Abstract

Publication types

MeSH terms

Substances

Grants and funding