A keratin cytoskeletal protein regulates protein synthesis and epithelial cell growth

Seyun Kim, Pauline Wong, Pierre A. Coulombe

Research output: Contribution to journalArticle

Abstract

Cell growth, an increase in mass and size, is a highly regulated cellular event. The Akt/mTOR (mammalian target of rapamycin) signalling pathway has a central role in the control of protein synthesis and thus the growth of cells, tissues and organisms. A striking example of a physiological context requiring rapid cell growth is tissue repair in response to injury. Here we show that keratin 17, an intermediate filament protein rapidly induced in wounded stratified epithelia, regulates cell growth through binding to the adaptor protein 14-3-3σ. Mouse skin keratinocytes lacking keratin 17 (ref. 4) show depressed protein translation and are of smaller size, correlating with decreased Akt/mTOR signalling activity. Other signalling kinases have normal activity, pointing to the specificity of this defect. Two amino acid residues located in the amino-terminal head domain of keratin 17 are required for the serum-dependent relocalization of 14-3-3σ from the nucleus to the cytoplasm, and for the concomitant stimulation of mTOR activity and cell growth. These findings reveal a new and unexpected role for the intermediate filament cytoskeleton in influencing cell growth and size by regulating protein synthesis.

Original languageEnglish (US)
Pages (from-to)362-365
Number of pages4
JournalNature
Volume441
Issue number7091
DOIs
StatePublished - May 18 2006

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Cytoskeletal Proteins
Keratins
Keratin-17
Epithelial Cells
Growth
Proteins
Cell Enlargement
14-3-3 Proteins
Intermediate Filament Proteins
Intermediate Filaments
Protein Biosynthesis
Sirolimus
Cytoskeleton
Keratinocytes
Cytoplasm
Phosphotransferases
Epithelium
Head
Amino Acids
Skin

ASJC Scopus subject areas

  • General

Cite this

A keratin cytoskeletal protein regulates protein synthesis and epithelial cell growth. / Kim, Seyun; Wong, Pauline; Coulombe, Pierre A.

In: Nature, Vol. 441, No. 7091, 18.05.2006, p. 362-365.

Research output: Contribution to journalArticle

Kim, Seyun ; Wong, Pauline ; Coulombe, Pierre A. / A keratin cytoskeletal protein regulates protein synthesis and epithelial cell growth. In: Nature. 2006 ; Vol. 441, No. 7091. pp. 362-365.
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