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

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

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32 Scopus citations

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.

Original language	English (US)
Article number	e1501290
Journal	Science Advances
Volume	2
Issue number	4
DOIs	https://doi.org/10.1126/sciadv.1501290
State	Published - Apr 2016
Externally published	Yes

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Hossain, M. B., Shifat, R., Johnson, D. G., Bedford, M. T., Gabrusiewicz, K. R., Cortes-Santiago, N., Luo, X., Lu, Z., Ezhilarasan, R., Sulman, E. P., Jiang, H., Li, S. S. C., Lang, F. F., Tyler, J., Hung, M. C., Fueyo, J., & Gomez-Manzano, C. (2016). TIE2-mediated tyrosine phosphorylation of H4 regulates DNA damage response by recruiting ABL1. Science Advances, 2(4), Article e1501290. https://doi.org/10.1126/sciadv.1501290

Hossain, MB, Shifat, R, Johnson, DG, Bedford, MT, Gabrusiewicz, KR, Cortes-Santiago, N, Luo, X, Lu, Z, Ezhilarasan, R, Sulman, EP, Jiang, H, Li, SSC, Lang, FF, Tyler, J, Hung, MC, Fueyo, J & Gomez-Manzano, C 2016, 'TIE2-mediated tyrosine phosphorylation of H4 regulates DNA damage response by recruiting ABL1', Science Advances, vol. 2, no. 4, e1501290. https://doi.org/10.1126/sciadv.1501290

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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.",

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

Abstract

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