IFNγ-induced suppression of β-catenin signaling : evidence for roles of Akt and 14.3.3ζ
© 2014 Nava, Kamekura, Quirós, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0)..
The proinflammatory cytokine interferon γ (IFNγ ) influences intestinal epithelial cell (IEC) homeostasis in a biphasic manner by acutely stimulating proliferation that is followed by sustained inhibition of proliferation despite continued mucosal injury. β-Catenin activation has been classically associated with increased IEC proliferation. However, we observed that IFNγ inhibits IEC proliferation despite sustained activation of Akt/β-catenin signaling. Here we show that inhibition of Akt/β-catenin-mediated cell proliferation by IFNγ is associated with the formation of a protein complex containing phosphorylated β-catenin 552 (pβ-cat552) and 14.3.3ζ. Akt1 served as a bimodal switch that promotes or inhibits β-catenin transactivation in response to IFNγ stimulation. IFNγ initially promotes β-catenin transactivation through Akt-dependent C-terminal phosphorylation of β-catenin to promote its association with 14.3.3ζ. Augmented β-catenin transactivation leads to increased Akt1 protein levels, and active Akt1 accumulates in the nucleus, where it phosphorylates 14.3.3ζ to translocate 14.3.3ζ/β-catenin from the nucleus, thereby inhibiting β-catenin transactivation and IEC proliferation. These results outline a dual function of Akt1 that suppresses IEC proliferation during intestinal inflammation.
Medienart: |
E-Artikel |
---|
Erscheinungsjahr: |
2014 |
---|---|
Erschienen: |
2014 |
Enthalten in: |
Zur Gesamtaufnahme - volume:25 |
---|---|
Enthalten in: |
Molecular biology of the cell - 25(2014), 19 vom: 01. Okt., Seite 2894-904 |
Sprache: |
Englisch |
---|
Beteiligte Personen: |
Nava, Porfirio [VerfasserIn] |
---|
Links: |
---|
Anmerkungen: |
Date Completed 10.06.2015 Date Revised 21.10.2021 published: Print-Electronic Citation Status MEDLINE |
---|
doi: |
10.1091/mbc.E13-09-0512 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
NLM240580958 |
---|
LEADER | 01000naa a22002652 4500 | ||
---|---|---|---|
001 | NLM240580958 | ||
003 | DE-627 | ||
005 | 20231224122418.0 | ||
007 | cr uuu---uuuuu | ||
008 | 231224s2014 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.1091/mbc.E13-09-0512 |2 doi | |
028 | 5 | 2 | |a pubmed24n0802.xml |
035 | |a (DE-627)NLM240580958 | ||
035 | |a (NLM)25079689 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Nava, Porfirio |e verfasserin |4 aut | |
245 | 1 | 0 | |a IFNγ-induced suppression of β-catenin signaling |b evidence for roles of Akt and 14.3.3ζ |
264 | 1 | |c 2014 | |
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 10.06.2015 | ||
500 | |a Date Revised 21.10.2021 | ||
500 | |a published: Print-Electronic | ||
500 | |a Citation Status MEDLINE | ||
520 | |a © 2014 Nava, Kamekura, Quirós, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). | ||
520 | |a The proinflammatory cytokine interferon γ (IFNγ ) influences intestinal epithelial cell (IEC) homeostasis in a biphasic manner by acutely stimulating proliferation that is followed by sustained inhibition of proliferation despite continued mucosal injury. β-Catenin activation has been classically associated with increased IEC proliferation. However, we observed that IFNγ inhibits IEC proliferation despite sustained activation of Akt/β-catenin signaling. Here we show that inhibition of Akt/β-catenin-mediated cell proliferation by IFNγ is associated with the formation of a protein complex containing phosphorylated β-catenin 552 (pβ-cat552) and 14.3.3ζ. Akt1 served as a bimodal switch that promotes or inhibits β-catenin transactivation in response to IFNγ stimulation. IFNγ initially promotes β-catenin transactivation through Akt-dependent C-terminal phosphorylation of β-catenin to promote its association with 14.3.3ζ. Augmented β-catenin transactivation leads to increased Akt1 protein levels, and active Akt1 accumulates in the nucleus, where it phosphorylates 14.3.3ζ to translocate 14.3.3ζ/β-catenin from the nucleus, thereby inhibiting β-catenin transactivation and IEC proliferation. These results outline a dual function of Akt1 that suppresses IEC proliferation during intestinal inflammation | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Research Support, N.I.H., Extramural | |
650 | 4 | |a Research Support, Non-U.S. Gov't | |
650 | 7 | |a 14-3-3 Proteins |2 NLM | |
650 | 7 | |a 14-3-3zeta protein, mouse |2 NLM | |
650 | 7 | |a beta Catenin |2 NLM | |
650 | 7 | |a Interferon-gamma |2 NLM | |
650 | 7 | |a 82115-62-6 |2 NLM | |
650 | 7 | |a Akt1 protein, mouse |2 NLM | |
650 | 7 | |a EC 2.7.11.1 |2 NLM | |
650 | 7 | |a Proto-Oncogene Proteins c-akt |2 NLM | |
650 | 7 | |a EC 2.7.11.1 |2 NLM | |
700 | 1 | |a Kamekura, Ryuta |e verfasserin |4 aut | |
700 | 1 | |a Quirós, Miguel |e verfasserin |4 aut | |
700 | 1 | |a Medina-Contreras, Oscar |e verfasserin |4 aut | |
700 | 1 | |a Hamilton, Ross W |e verfasserin |4 aut | |
700 | 1 | |a Kolegraff, Keli N |e verfasserin |4 aut | |
700 | 1 | |a Koch, Stefan |e verfasserin |4 aut | |
700 | 1 | |a Candelario, Aurora |e verfasserin |4 aut | |
700 | 1 | |a Romo-Parra, Hector |e verfasserin |4 aut | |
700 | 1 | |a Laur, Oskar |e verfasserin |4 aut | |
700 | 1 | |a Hilgarth, Roland S |e verfasserin |4 aut | |
700 | 1 | |a Denning, Timothy L |e verfasserin |4 aut | |
700 | 1 | |a Parkos, Charles A |e verfasserin |4 aut | |
700 | 1 | |a Nusrat, Asma |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t Molecular biology of the cell |d 1992 |g 25(2014), 19 vom: 01. Okt., Seite 2894-904 |w (DE-627)NLM012640255 |x 1939-4586 |7 nnns |
773 | 1 | 8 | |g volume:25 |g year:2014 |g number:19 |g day:01 |g month:10 |g pages:2894-904 |
856 | 4 | 0 | |u http://dx.doi.org/10.1091/mbc.E13-09-0512 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 25 |j 2014 |e 19 |b 01 |c 10 |h 2894-904 |