uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Proteolytic Histone Modification by Mast Cell Tryptase, a Serglycin Proteoglycan-dependent Secretory Granule Protease
Swedish Univ Agr Sci, Dept Anat Physiol & Biochem, S-75123 Uppsala, Sweden..
Univ Trieste, Dept Life Sci, I-34127 Trieste, Italy..
Hebrew Univ Jerusalem, Fac Med, Inst Drug Res, Dept Pharmacol, IL-91120 Jerusalem, Israel..
Hebrew Univ Jerusalem, Fac Med, Inst Drug Res, Dept Pharmacol, IL-91120 Jerusalem, Israel..
Show others and affiliations
2014 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 289, no 11, 7682-7690 p.Article in journal (Refereed) Published
Abstract [en]

Background: Tryptase is a serglycin proteoglycan-dependent protease localized in mast cell granules. Results: Tryptase was found to degrade core histones, both during apoptosis and in viable cells. Conclusion: A serglycin-tryptase axis is identified as a novel mechanism for histone modification. Significance: Secretory granule compounds are implicated in the regulation of nuclear events. A hallmark feature of mast cells is their high content of cytoplasmic secretory granules filled with various preformed compounds, including proteases of tryptase-, chymase-, and carboxypeptidase A3 type that are electrostatically bound to serglycin proteoglycan. Apart from participating in extracellular processes, serglycin proteoglycan and one of its associated proteases, tryptase, are known to regulate cell death by promoting apoptosis over necrosis. Here we sought to outline the underlying mechanism and identify core histones as primary proteolytic targets for the serglycin-tryptase axis. During the cell death process, tryptase was found to relocalize from granules into the cytosol and nucleus, and it was found that the absence of tryptase was associated with a pronounced accumulation of core histones both in the cytosol and in the nucleus. Intriguingly, tryptase deficiency resulted in defective proteolytic modification of core histones even at baseline conditions, i.e. in the absence of cytotoxic agent, suggesting that tryptase has a homeostatic impact on nuclear events. Indeed, tryptase was found in the nucleus of viable cells and was shown to cleave core histones in their N-terminal tail. Moreover, it was shown that the absence of the serglycin-tryptase axis resulted in altered chromatin composition. Together, these findings implicate histone proteolysis through a secretory granule-derived serglycin-tryptase axis as a novel principle for histone modification, during both cell homeostasis and cell death.

Place, publisher, year, edition, pages
2014. Vol. 289, no 11, 7682-7690 p.
Keyword [en]
Apoptosis, Histone Modification, Mast Cell, Protease, Proteoglycan, Proteolytic Enzymes, mMCP-6, Secretory Granules, Serglycin, Tryptase
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:uu:diva-316863DOI: 10.1074/jbc.M113.546895ISI: 000332761500036PubMedID: 24478313OAI: oai:DiVA.org:uu-316863DiVA: diva2:1079167
Funder
Swedish Research CouncilSwedish Cancer Society
Available from: 2017-03-07 Created: 2017-03-07 Last updated: 2017-03-07Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Pejler, Gunnar
In the same journal
Journal of Biological Chemistry
Cancer and Oncology

Search outside of DiVA

GoogleGoogle Scholar

Altmetric score

Total: 9 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf