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Cooperative role of MMP‐3 and HP1 in heat shock protein transcription
Author(s) -
Eguchi Takanori,
Calderwood Stuart
Publication year - 2013
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.27.1_supplement.977.1
Subject(s) - hsf1 , heterochromatin protein 1 , heat shock factor , transcription factor , heat shock protein , microbiology and biotechnology , transfection , hsp70 , biology , heat shock , chemistry , heterochromatin , gene , chromatin , biochemistry
Transcriptional induction of HSP70 is controlled by stress responsed phosphorylation of heat shock transcription factor (HSF1) (1). Here we report novel transcriptional induction system of HSP70 mediated by cooperative action of heterochromation protein (HP1) and intracellular matrix metalloprotease‐3 (MMP‐3). MMP family have been studied as extracellular proteases; however, a recent study revealed a novel role of MMP‐3 in transcription in cellular nuclei and direct interaction between MMP‐3 and HP1 (2). HP1 family was firstly discovered as a heterochromatin forming factors; however, HP1 is a versatile protein involving also in transcription activation upon heat stress in drosophila. In this study, transcriptome analysis in MMP3‐transfected HEK293 cells, HSP70B was revealed as the most inducible factor by intracellular MMP3 among whole mRNA. By deletion mutant analysis, full length and PEX domain of MMP3 induced HSP70B mRNA. Co‐transfection studies revealed cooperation between the PEX and HP1 for Hsp70B mRNA induction and promoter activation. HSF1 enhanced the action of MMP3 activating the Hsp70B promoter in reporter assay but dominant negative HSF1 reversed it, suggesting crucial interaction between these proteins. Overexpressed PEX domain co‐localized with HP1 and remarkably accumulated into nucler stress bodies upon heat stress observed in immunocytochemistry. Furthermore, HP1 remarkably reduced clonogenicity of HeLa cells, while knock down of MMP‐3 repressed proliferation in HCS‐2/8 cells. Together with these results, it was clarified that MMP3 and HP1 transcriptinally induce HSP70 and are involed in stress response and tumorigenesis.