Cell density-dependent proteolysis by HtrA1 induces translocation of zyxin to the nucleus and increased cell survival
Proteases modulate critical processes in cutaneous tissue repair to orchestrate inflammation, cell proliferation and tissue remodeling. However, the functional consequences and implications in healing impairments of most cleavage events are not understood. Using iTRAQ-based Terminal Amine Isotopic Labeling of Substrates (TAILS) we had characterized proteolytic signatures in a porcine wound healing model and identified two neo-N termini derived from proteolytic cleavage of the focal adhesion protein and mechanotransducer zyxin. Here, we assign these proteolytic events to the activity of either caspase-1 or serine protease HtrA1 and analyze the biological relevance of the resultant zyxin truncations. By cellular expression of full-length and truncated zyxin proteins, we demonstrate nuclear translocation of a C-terminal zyxin fragment that could also be generated in vitro by HtrA1 cleavage and provide evidence for its anti-apoptotic activities, potentially by regulating the expression of modulators of cell proliferation, protein synthesis and genome stability. Targeted degradomics correlated endogenous generation of the same zyxin fragment with increased cell density in human primary dermal fibroblasts. Hence, this newly identified HtrA1-zyxin protease signaling axis might present a novel mechanism to transiently enhance cell survival in environments of increased cell density like in wound granulation tissue.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2020 |
|---|---|
| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:11 |
|---|---|
| Enthalten in: |
Cell death & disease - 11(2020), 8 vom: 21. Aug., Seite 674 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Sabino, Fabio [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
EC 3.4.- |
|---|
| Anmerkungen: |
Date Completed 13.04.2021 Date Revised 13.12.2023 published: Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1038/s41419-020-02883-2 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM314005277 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM314005277 | ||
| 003 | DE-627 | ||
| 005 | 20231227130324.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2020 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1038/s41419-020-02883-2 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1224.xml |
| 035 | |a (DE-627)NLM314005277 | ||
| 035 | |a (NLM)32826880 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Sabino, Fabio |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Cell density-dependent proteolysis by HtrA1 induces translocation of zyxin to the nucleus and increased cell survival |
| 264 | 1 | |c 2020 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 13.04.2021 | ||
| 500 | |a Date Revised 13.12.2023 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Proteases modulate critical processes in cutaneous tissue repair to orchestrate inflammation, cell proliferation and tissue remodeling. However, the functional consequences and implications in healing impairments of most cleavage events are not understood. Using iTRAQ-based Terminal Amine Isotopic Labeling of Substrates (TAILS) we had characterized proteolytic signatures in a porcine wound healing model and identified two neo-N termini derived from proteolytic cleavage of the focal adhesion protein and mechanotransducer zyxin. Here, we assign these proteolytic events to the activity of either caspase-1 or serine protease HtrA1 and analyze the biological relevance of the resultant zyxin truncations. By cellular expression of full-length and truncated zyxin proteins, we demonstrate nuclear translocation of a C-terminal zyxin fragment that could also be generated in vitro by HtrA1 cleavage and provide evidence for its anti-apoptotic activities, potentially by regulating the expression of modulators of cell proliferation, protein synthesis and genome stability. Targeted degradomics correlated endogenous generation of the same zyxin fragment with increased cell density in human primary dermal fibroblasts. Hence, this newly identified HtrA1-zyxin protease signaling axis might present a novel mechanism to transiently enhance cell survival in environments of increased cell density like in wound granulation tissue | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Proteome |2 NLM | |
| 650 | 7 | |a ZYX protein, human |2 NLM | |
| 650 | 7 | |a Zyxin |2 NLM | |
| 650 | 7 | |a Peptide Hydrolases |2 NLM | |
| 650 | 7 | |a EC 3.4.- |2 NLM | |
| 650 | 7 | |a High-Temperature Requirement A Serine Peptidase 1 |2 NLM | |
| 650 | 7 | |a EC 3.4.21.- |2 NLM | |
| 650 | 7 | |a HTRA1 protein, human |2 NLM | |
| 650 | 7 | |a EC 3.4.21.- |2 NLM | |
| 700 | 1 | |a Madzharova, Elizabeta |e verfasserin |4 aut | |
| 700 | 1 | |a Auf dem Keller, Ulrich |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Cell death & disease |d 2010 |g 11(2020), 8 vom: 21. Aug., Seite 674 |w (DE-627)NLM202030881 |x 2041-4889 |7 nnns |
| 773 | 1 | 8 | |g volume:11 |g year:2020 |g number:8 |g day:21 |g month:08 |g pages:674 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1038/s41419-020-02883-2 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 11 |j 2020 |e 8 |b 21 |c 08 |h 674 | ||