Academic Journal
Sumoylation by Ubc9 Regulates the Stem Cell Compartment and Structure and Function of the Intestinal Epithelium in Mice
| العنوان: | Sumoylation by Ubc9 Regulates the Stem Cell Compartment and Structure and Function of the Intestinal Epithelium in Mice |
|---|---|
| المؤلفون: | Demarque, M.D., Nacerddine, K., Neyret-Kahn, H., Andrieux, A., Danenberg, E.M., Jouvion, G., Bomme, P., Hamard, G., Romagnolo, B., Terris, B., Cumano, A., Barker, N., Clevers, H., Dejean, A. |
| المصدر: | Demarque , M D , Nacerddine , K , Neyret-Kahn , H , Andrieux , A , Danenberg , E M , Jouvion , G , Bomme , P , Hamard , G , Romagnolo , B , Terris , B , Cumano , A , Barker , N , Clevers , H & Dejean , A 2010 , ' Sumoylation by Ubc9 Regulates the Stem Cell Compartment and Structure and Function of the Intestinal Epithelium in Mice ' , Gastroenterology , vol. 140 , no. 1 , pp. 286-296 . https://doi.org/10.1053/j.gastro.2010.10.002 |
| سنة النشر: | 2010 |
| المجموعة: | KNAW: Research Explorer (Koninklijke Nederlandse Akademie van Wetenschappen / Royal Netherlands Academy of Arts and Sciences) |
| الوصف: | BACKGROUND & AIMS:: Small ubiquitin-like modifiers (SUMOs) are attached to other proteins to regulate their function (sumoylation). We investigated the role of Ubc9, which covalently attaches SUMOs to proteins, in the gastrointestinal tract of adult mice. METHODS:: We investigated the effects of decreased sumoylation in adult mammals by generating mice with an inducible knockout (by injection of 4-hydroxytamoxifen) of the E2 enzyme Ubc9 (Ubc9fl/-/ROSA26-CreERT2 mice). We analyzed the phenotypes using a range of histologic techniques. RESULTS:: Loss of Ubc9 from adult mice primarily affected the small intestine. Ubc9fl/-/ROSA26-CreERT2 mice died within 6 days of 4-hydroxytamoxifen injection, losing 20% or less of their body weight and developing severe diarrhea on the second day after injection. Surprisingly, other epithelial tissues appeared to be unaffected at that stage. Decreased sumoylation led to the depletion of the intestinal proliferative compartment and to the rapid disappearance of stem cells. Sumoylation was required to separate the proliferative and differentiated compartments from the crypt and control differentiation and function of the secretory lineage. Sumoylation was required for nucleus positioning and polarized organization of actin in the enterocytes. Loss of sumoylation caused detachment of the enterocytes from the basal lamina, as observed in tissue fragility diseases. We identified the intermediate filament keratin 8 as a SUMO substrate in epithelial cells. CONCLUSIONS:: Sumoylation maintains intestinal stem cells and the architecture, mechanical stability, and function of the intestinal epithelium of mice. ; BACKGROUND & AIMS:: Small ubiquitin-like modifiers (SUMOs) are attached to other proteins to regulate their function (sumoylation). We investigated the role of Ubc9, which covalently attaches SUMOs to proteins, in the gastrointestinal tract of adult mice. METHODS:: We investigated the effects of decreased sumoylation in adult mammals by generating mice with an inducible ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | https://pure.knaw.nl/portal/en/publications/da17021f-e744-49c0-8536-f3a3b22b5e32 |
| DOI: | 10.1053/j.gastro.2010.10.002 |
| الاتاحة: | https://pure.knaw.nl/portal/en/publications/da17021f-e744-49c0-8536-f3a3b22b5e32 https://doi.org/10.1053/j.gastro.2010.10.002 https://hdl.handle.net/20.500.11755/da17021f-e744-49c0-8536-f3a3b22b5e32 |
| Rights: | info:eu-repo/semantics/restrictedAccess |
| رقم الانضمام: | edsbas.D56ED017 |
| قاعدة البيانات: | BASE |
| ResultId |
1 |
|---|---|
| Header |
edsbas BASE edsbas.D56ED017 771 3 Academic Journal academicJournal 771.324340820313 |
| PLink |
https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&scope=site&db=edsbas&AN=edsbas.D56ED017&custid=s6537998&authtype=sso |
| FullText |
Array
(
[Availability] => 0
)
Array ( [0] => Array ( [Url] => https://pure.knaw.nl/portal/en/publications/da17021f-e744-49c0-8536-f3a3b22b5e32# [Name] => EDS - BASE [Category] => fullText [Text] => View record in BASE [MouseOverText] => View record in BASE ) ) |
| Items |
Array
(
[Name] => Title
[Label] => Title
[Group] => Ti
[Data] => Sumoylation by Ubc9 Regulates the Stem Cell Compartment and Structure and Function of the Intestinal Epithelium in Mice
)
Array ( [Name] => Author [Label] => Authors [Group] => Au [Data] => <searchLink fieldCode="AR" term="%22Demarque%2C+M%2ED%2E%22">Demarque, M.D.</searchLink><br /><searchLink fieldCode="AR" term="%22Nacerddine%2C+K%2E%22">Nacerddine, K.</searchLink><br /><searchLink fieldCode="AR" term="%22Neyret-Kahn%2C+H%2E%22">Neyret-Kahn, H.</searchLink><br /><searchLink fieldCode="AR" term="%22Andrieux%2C+A%2E%22">Andrieux, A.</searchLink><br /><searchLink fieldCode="AR" term="%22Danenberg%2C+E%2EM%2E%22">Danenberg, E.M.</searchLink><br /><searchLink fieldCode="AR" term="%22Jouvion%2C+G%2E%22">Jouvion, G.</searchLink><br /><searchLink fieldCode="AR" term="%22Bomme%2C+P%2E%22">Bomme, P.</searchLink><br /><searchLink fieldCode="AR" term="%22Hamard%2C+G%2E%22">Hamard, G.</searchLink><br /><searchLink fieldCode="AR" term="%22Romagnolo%2C+B%2E%22">Romagnolo, B.</searchLink><br /><searchLink fieldCode="AR" term="%22Terris%2C+B%2E%22">Terris, B.</searchLink><br /><searchLink fieldCode="AR" term="%22Cumano%2C+A%2E%22">Cumano, A.</searchLink><br /><searchLink fieldCode="AR" term="%22Barker%2C+N%2E%22">Barker, N.</searchLink><br /><searchLink fieldCode="AR" term="%22Clevers%2C+H%2E%22">Clevers, H.</searchLink><br /><searchLink fieldCode="AR" term="%22Dejean%2C+A%2E%22">Dejean, A.</searchLink> ) Array ( [Name] => TitleSource [Label] => Source [Group] => Src [Data] => Demarque , M D , Nacerddine , K , Neyret-Kahn , H , Andrieux , A , Danenberg , E M , Jouvion , G , Bomme , P , Hamard , G , Romagnolo , B , Terris , B , Cumano , A , Barker , N , Clevers , H & Dejean , A 2010 , ' Sumoylation by Ubc9 Regulates the Stem Cell Compartment and Structure and Function of the Intestinal Epithelium in Mice ' , Gastroenterology , vol. 140 , no. 1 , pp. 286-296 . https://doi.org/10.1053/j.gastro.2010.10.002 ) Array ( [Name] => DatePubCY [Label] => Publication Year [Group] => Date [Data] => 2010 ) Array ( [Name] => Subset [Label] => Collection [Group] => HoldingsInfo [Data] => KNAW: Research Explorer (Koninklijke Nederlandse Akademie van Wetenschappen / Royal Netherlands Academy of Arts and Sciences) ) Array ( [Name] => Abstract [Label] => Description [Group] => Ab [Data] => BACKGROUND & AIMS:: Small ubiquitin-like modifiers (SUMOs) are attached to other proteins to regulate their function (sumoylation). We investigated the role of Ubc9, which covalently attaches SUMOs to proteins, in the gastrointestinal tract of adult mice. METHODS:: We investigated the effects of decreased sumoylation in adult mammals by generating mice with an inducible knockout (by injection of 4-hydroxytamoxifen) of the E2 enzyme Ubc9 (Ubc9fl/-/ROSA26-CreERT2 mice). We analyzed the phenotypes using a range of histologic techniques. RESULTS:: Loss of Ubc9 from adult mice primarily affected the small intestine. Ubc9fl/-/ROSA26-CreERT2 mice died within 6 days of 4-hydroxytamoxifen injection, losing 20% or less of their body weight and developing severe diarrhea on the second day after injection. Surprisingly, other epithelial tissues appeared to be unaffected at that stage. Decreased sumoylation led to the depletion of the intestinal proliferative compartment and to the rapid disappearance of stem cells. Sumoylation was required to separate the proliferative and differentiated compartments from the crypt and control differentiation and function of the secretory lineage. Sumoylation was required for nucleus positioning and polarized organization of actin in the enterocytes. Loss of sumoylation caused detachment of the enterocytes from the basal lamina, as observed in tissue fragility diseases. We identified the intermediate filament keratin 8 as a SUMO substrate in epithelial cells. CONCLUSIONS:: Sumoylation maintains intestinal stem cells and the architecture, mechanical stability, and function of the intestinal epithelium of mice. ; BACKGROUND & AIMS:: Small ubiquitin-like modifiers (SUMOs) are attached to other proteins to regulate their function (sumoylation). We investigated the role of Ubc9, which covalently attaches SUMOs to proteins, in the gastrointestinal tract of adult mice. METHODS:: We investigated the effects of decreased sumoylation in adult mammals by generating mice with an inducible ... ) Array ( [Name] => TypeDocument [Label] => Document Type [Group] => TypDoc [Data] => article in journal/newspaper ) Array ( [Name] => Language [Label] => Language [Group] => Lang [Data] => English ) Array ( [Name] => NoteTitleSource [Label] => Relation [Group] => SrcInfo [Data] => https://pure.knaw.nl/portal/en/publications/da17021f-e744-49c0-8536-f3a3b22b5e32 ) Array ( [Name] => DOI [Label] => DOI [Group] => ID [Data] => 10.1053/j.gastro.2010.10.002 ) Array ( [Name] => URL [Label] => Availability [Group] => URL [Data] => https://pure.knaw.nl/portal/en/publications/da17021f-e744-49c0-8536-f3a3b22b5e32<br />https://doi.org/10.1053/j.gastro.2010.10.002<br />https://hdl.handle.net/20.500.11755/da17021f-e744-49c0-8536-f3a3b22b5e32 ) Array ( [Name] => Copyright [Label] => Rights [Group] => Cpyrght [Data] => info:eu-repo/semantics/restrictedAccess ) Array ( [Name] => AN [Label] => Accession Number [Group] => ID [Data] => edsbas.D56ED017 ) |
| RecordInfo |
Array
(
[BibEntity] => Array
(
[Identifiers] => Array
(
[0] => Array
(
[Type] => doi
[Value] => 10.1053/j.gastro.2010.10.002
)
)
[Languages] => Array
(
[0] => Array
(
[Text] => English
)
)
[Titles] => Array
(
[0] => Array
(
[TitleFull] => Sumoylation by Ubc9 Regulates the Stem Cell Compartment and Structure and Function of the Intestinal Epithelium in Mice
[Type] => main
)
)
)
[BibRelationships] => Array
(
[HasContributorRelationships] => Array
(
[0] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Demarque, M.D.
)
)
)
[1] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Nacerddine, K.
)
)
)
[2] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Neyret-Kahn, H.
)
)
)
[3] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Andrieux, A.
)
)
)
[4] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Danenberg, E.M.
)
)
)
[5] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Jouvion, G.
)
)
)
[6] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Bomme, P.
)
)
)
[7] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Hamard, G.
)
)
)
[8] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Romagnolo, B.
)
)
)
[9] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Terris, B.
)
)
)
[10] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Cumano, A.
)
)
)
[11] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Barker, N.
)
)
)
[12] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Clevers, H.
)
)
)
[13] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Dejean, A.
)
)
)
)
[IsPartOfRelationships] => Array
(
[0] => Array
(
[BibEntity] => Array
(
[Dates] => Array
(
[0] => Array
(
[D] => 01
[M] => 01
[Type] => published
[Y] => 2010
)
)
[Identifiers] => Array
(
[0] => Array
(
[Type] => issn-locals
[Value] => edsbas
)
)
[Titles] => Array
(
[0] => Array
(
[TitleFull] => $2
[Type] => main
)
)
)
)
)
)
)
|
| IllustrationInfo |