spacer gif spacer gif spacer gif spacer gif Propose a workshop for 2011 spacer gif
QUICK SEARCH:   [advanced]


spacer gif
     Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents    

This Article
Right arrow Figures Only
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Related articles in JCS
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Reichelt, J.
Right arrow Articles by Magin, T. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Reichelt, J.
Right arrow Articles by Magin, T. M.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?
Journal of Cell Science 115, 2639-2650 (2002)
© 2002 The Company of Biologists Limited

Research Article

Hyperproliferation, induction of c-Myc and 14-3-3{sigma}, but no cell fragility in keratin-10-null mice

Julia Reichelt and Thomas M. Magin*

Institute of Physiological Chemistry and Bonner Forum Biomedizin, University of Bonn, Nussallee 11, 53115 Bonn, Germany

* Author for correspondence (e-mail: t.magin{at}uni-bonn.de )

Accepted 12 April 2002

In the past, keratins have been established as structural proteins. Indeed, mutations in keratin 10 (K10) and other epidermal keratins lead to severe skin fragility syndromes. Here, we present adult K10-/- mice, which reveal a novel connection between the regulation of cell proliferation and K10. Unlike most keratin mutant mice, the epidermis of adult K10-/- mice showed no cytolysis but displayed hyperproliferation of basal keratinocytes and an increased cell size. BrdU labelling revealed a shortened transition time for keratinocytes migrating outwards and DAPI staining of epidermal sheets uncovered an impaired organization of epidermal proliferation units. These remarkable changes were accompanied by the induction of c-Myc, cyclin D1, 14-3-3{sigma} and of wound healing keratins K6 and K16. The phosphorylation of Rb remained unaltered. In line with the downregulation of K10 in squamous cell carcinomas and its absence in proliferating cells in vivo, our data suggest that the tissue-restricted expression of some members of the keratin gene family not only serves structural functions. Our results imply that the altered composition of the suprabasal cytoskeleton is able to alter the proliferation state of basal cells through the induction of c-Myc. A previous model based on transfection of K10 in immortalized human keratinocytes suggested a direct involvement of K10 in cell cycle control. While those experiments were performed in human cultured keratinocytes, our data establish, that in vivo, K10 acts by an indirect control mechanism in trans.

Key words: Keratins, c-Myc, 14-3-3 proteins, Epidermis, Cell proliferation


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?

Related articles in JCS:

A novel role for keratin 10

JCS 2002 115: 1303. [Full Text]  



This article has been cited by other articles:


Home page
 JCBHome page
P. Vijayaraj, C. Kroger, U. Reuter, R. Windoffer, R. E. Leube, and T. M. Magin
Keratins regulate protein biosynthesis through localization of GLUT1 and -3 upstream of AMP kinase and Raptor
J. Cell Biol., October 19, 2009; 187(2): 175 - 184.
[Abstract] [Full Text] [PDF]

Home page
 JCBHome page
S. Getsios, C. L. Simpson, S.-i. Kojima, R. Harmon, L. J. Sheu, R. L. Dusek, M. Cornwell, and K. J. Green
Desmoglein 1-dependent suppression of EGFR signaling promotes epidermal differentiation and morphogenesis
J. Cell Biol., June 29, 2009; 185(7): 1243 - 1258.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
M. L. Kerns, D. DePianto, A. T. Dinkova-Kostova, P. Talalay, and P. A. Coulombe
Reprogramming of keratin biosynthesis by sulforaphane restores skin integrity in epidermolysis bullosa simplex
PNAS, September 4, 2007; 104(36): 14460 - 14465.
[Abstract] [Full Text] [PDF]

Home page
 Genes Dev.Home page
S. Kim and P. A. Coulombe
Intermediate filament scaffolds fulfill mechanical, organizational, and signaling functions in the cytoplasm
Genes & Dev., July 1, 2007; 21(13): 1581 - 1597.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
J. M. Paramio, M. Santos, and J. L. Jorcano
The ends of a conundrum?
J. Cell Sci., April 1, 2007; 120(7): 1145 - 1147.
[Full Text] [PDF]

Home page
 Hum Mol GenetHome page
F. B. Muller, M. Huber, T. Kinaciyan, I. Hausser, C. Schaffrath, T. Krieg, D. Hohl, B. P. Korge, and M. J. Arin
A human keratin 10 knockout causes recessive epidermolytic hyperkeratosis
Hum. Mol. Genet., April 1, 2006; 15(7): 1133 - 1141.
[Abstract] [Full Text] [PDF]

Home page
 JCBHome page
P. Wong and P. A. Coulombe
Loss of keratin 6 (K6) proteins reveals a function for intermediate filaments during wound repair
J. Cell Biol., October 27, 2003; 163(2): 327 - 337.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. Santos, P. Perez, C. Segrelles, S. Ruiz, J. L. Jorcano, and J. M. Paramio
Impaired NF-kappa B Activation and Increased Production of Tumor Necrosis Factor alpha in Transgenic Mice Expressing Keratin K10 in the Basal Layer of the Epidermis
J. Biol. Chem., April 4, 2003; 278(15): 13422 - 13430.
[Abstract] [Full Text] [PDF]


© The Company of Biologists Ltd 2002