OpenSSL SSL_connect: Connection reset by peer in connection to v2.sherpa.ac.uk:443 PuSH - Publication Server of Helmholtz Zentrum München: Loss of intestinal crypt progenitor cells owing to inactivation of both Notch1 and Notch2 is accompanied by derepression of CDK inhibitors p27Kip1 and p57Kip2.

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Riccio, O.* ; van Gijn, M.E.* ; Bezdek, A.C.* ; Pellegrinet, L.* ; van Es, J.H.* ; Zimber-Strobl, U. ; Strobl, L.J. ; Honjo, T.* ; Clevers, H.* ; Radtke, F.*

Loss of intestinal crypt progenitor cells owing to inactivation of both Notch1 and Notch2 is accompanied by derepression of CDK inhibitors p27Kip1 and p57Kip2.

EMBO Rep. 9, 377-383 (2008)
DOI
Open Access Green as soon as Postprint is submitted to ZB.
The crucial role of individual Notch receptors and the mechanism by which they maintain intestinal crypt progenitor cells were assessed by using a series of inducible gut-specific Notch mutant mice. We found that Notch1 and Notch2 receptors function redundantly in the gut, as only simultaneous loss of both receptors results in complete conversion of proliferating crypt progenitors into post-mitotic goblet cells. This conversion correlates with the loss of Hes1 expression and derepression of the cyclin-dependent kinase (CDK) inhibitors p27Kip1 and p57Kip2. We also found that the promoter of both CDK inhibitor genes is occupied by the Notch effector Hes1 in wild-type crypt progenitor cells. Thus, our results indicate that Notch-mediated Hes1 expression contributes to the maintenance of the proliferative crypt compartment of the small intestine by transcriptionally repressing two CDK inhibitors.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Notch; intestine; CDKI; growth arrest; differentiation
ISSN (print) / ISBN 1469-221X
e-ISSN 1469-3178
Journal EMBO Reports
Quellenangaben Volume: 9, Issue: 4, Pages: 377-383 Article Number: , Supplement: ,
Publisher EMBO Press
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Research Unit Gene Vector (AGV)