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Subnuclear domain proteins in cancer cells support the functions of RUNX2 in the DNA damage response.
- Source :
-
Journal of cell science [J Cell Sci] 2015 Feb 15; Vol. 128 (4), pp. 728-40. Date of Electronic Publication: 2015 Jan 20. - Publication Year :
- 2015
-
Abstract
- Cancer cells exhibit modifications in nuclear architecture and transcriptional control. Tumor growth and metastasis are supported by RUNX family transcriptional scaffolding proteins, which mediate the assembly of nuclear-matrix-associated gene-regulatory hubs. We used proteomic analysis to identify RUNX2-dependent protein-protein interactions associated with the nuclear matrix in bone, breast and prostate tumor cell types and found that RUNX2 interacts with three distinct proteins that respond to DNA damage - RUVBL2, INTS3 and BAZ1B. Subnuclear foci containing these proteins change in intensity or number following UV irradiation. Furthermore, RUNX2, INTS3 and BAZ1B form UV-responsive complexes with the serine-139-phosphorylated isoform of H2AX (γH2AX). UV irradiation increases the interaction of BAZ1B with γH2AX and decreases histone H3 lysine 9 acetylation levels, which mark accessible chromatin. RUNX2 depletion prevents the BAZ1B-γH2AX interaction and attenuates loss of H3K9 and H3K56 acetylation. Our data are consistent with a model in which RUNX2 forms functional complexes with BAZ1B, RUVBL2 and INTS3 to mount an integrated response to DNA damage. This proposed cytoprotective function for RUNX2 in cancer cells might clarify its expression in chemotherapy-resistant and/or metastatic tumors.<br /> (© 2015. Published by The Company of Biologists Ltd.)
- Subjects :
- ATPases Associated with Diverse Cellular Activities
Acetylation
Bone Neoplasms genetics
Bone Neoplasms pathology
Cell Line, Tumor
Core Binding Factor Alpha 1 Subunit genetics
DNA Damage genetics
Histones metabolism
Humans
Multiprotein Complexes metabolism
Osteosarcoma genetics
Osteosarcoma pathology
Phosphorylation
RNA Interference
RNA, Small Interfering
Ultraviolet Rays
Carrier Proteins metabolism
Core Binding Factor Alpha 1 Subunit metabolism
DNA Helicases metabolism
DNA Repair genetics
DNA-Binding Proteins metabolism
Transcription Factors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1477-9137
- Volume :
- 128
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of cell science
- Publication Type :
- Academic Journal
- Accession number :
- 25609707
- Full Text :
- https://doi.org/10.1242/jcs.160051