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ID 56118
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Eguchi, Takanori Department of Dental Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences ORCID Kakenhi
Calderwood, Stuart K. Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School
Takigawa, Masaharu Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Dental School/Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Kubota, Satoshi Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Kozaki, Ken‐ichi Department of Dental Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Abstract
Matrix metalloproteinases (MMPs) are crucial factors in tumor progression, inflammatory/immune responses and tissue development/regeneration. Of note, it has been known that MMPs promote genome instability, epithelial-mesenchymal transition, invasion, and metastasis in tumor progression. We previously reported that human MMP3 could translocate into cellular nuclei and control transcription in human chondrosarcoma-derived cells and in articular cartilage (Eguchi et al. [2008] Mol Cell Biol 28(7):2391-2413); however, further transcriptional target genes and cofactors of intranuclear MMP3 have not been uncovered. In this paper, we used transcriptomics analysis in order to examine novel transcriptional target genes regulated by intracellular MMP3. We found that mRNA levels of HSP family members (HSP70B', HSP72, HSP40/DNAJ, and HSP20/CRYAB) are upregulated by the intracellular MMP3 overload. Bioinformatic analysis predicted several transcription factors that possibly interact with MMP3. Among these factors, heat shock factor 1 (HSF1) cooperated with the MMP3 to activate the HSP70B' gene promoter in reporter gene assays, while a dominant negative HSF1 blocked the role for MMP3 in the trans-activation. The hemopexin-like repeat (PEX) domain of the human MMP3 was essential for transcriptional induction of the HSP70B' gene. In addition, chromobox proteins CBX5/HP1α and CBX3/HP1γ cooperated with the PEX domain in induction of HSP70B' mRNA. Taken together, this study newly clarified that intracellular MMP3 cooperate with CBXs/HP1s in transcriptional promotion of HSP genes.
Keywords
CBXs
CHROMOBOX PROTEINS
HEAT SHOCK FACTOR 1
HEAT SHOCK PROTEINS
HETEROCHROMATIN PROTEINS
HP1
HSF1
HSPs
MATRIX METALLOPROTEINASE
MMP3
TRANSCRIPTION
Published Date
2016-05-21
Publication Title
Journal of Cellular Biochemistry
Volume
volume118
Issue
issue1
Publisher
Wiley
Start Page
43
End Page
51
ISSN
07302312
NCID
AA1052210X
Content Type
Journal Article
language
英語
OAI-PMH Set
岡山大学
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DOI
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isVersionOf https://doi.org/10.1002/jcb.25607