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Intra‐nuclear MMP‐3 controls transcription of HSP70 gene through interaction with heterochromatin proteins.
Author(s) -
Eguchi Takanori,
Calderwood Stuart
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.688.2
Subject(s) - mmp3 , transcription factor , microbiology and biotechnology , chromatin , matrix metalloproteinase , hsf1 , biology , heterochromatin protein 1 , transcription (linguistics) , heat shock protein , gene expression , heterochromatin , gene , chemistry , hsp70 , genetics , linguistics , philosophy
Matrix metalloproteinases (MMPs) have been shown to cleave extracellular proteins to play key roles in development, inflammatory diseases, neurodegenerative diseases and in cancer. Here we have examined an intracellular transcriptional role for nuclear MMP3. Intracellular MMP3 appeared to regulate transcriptional and signaling networks in a range of genes, most notably molecular chaperone HSP70B. MMP3 regulated HSP70B transcription through interaction with chromatin and heterochromatin proteins (HP1) including HP1α and HP1γ. Inter‐molecular interaction between MMP3 and HP1alpha was increased by heat stress in 5 min (Fig. 2). The PEX domain of MMP3 was accumulated into nuclei upon heat stress (Fig. 2). HSP70B was shown previously to be regulated exclusively by transcription factor HSF1, and here we have shown MMP3 and the HP1s to synergize with this factor. Our experiments thus suggested a novel function for MMP3 in stimulating transcription of HSP70B and these findings might suggest a role for MMP3 in cancer and inflammatory diseases in addition to its established extracellular protease function.