Immortalization of primary human keratinocytes by the helix-loop-helix protein, Id-1

Rhoda M. Alani, Jens Hasskarl, Miranda Grace, Maria Clementia Hernandez, Mark A. Israel, Karl Münger

Research output: Contribution to journalArticlepeer-review

151 Scopus citations

Abstract

Basic helix-loop-helix (bHLH) DNA-binding proteins have been demonstrated to regulate tissue-specific transcription within multiple cell lineages. The Id family of helix-loop-helix proteins does not possess a basic DNA-binding domain and functions as a negative regulator of bHLH proteins. Overexpression of Id proteins with a variety of cell types has been shown to inhibit their ability to differentiate under appropriate conditions. We demonstrate that ectopic expression of Id-1 leads to activation of telomerase activity and immortalization of primary human keratinocytes. These immortalized cells have a decreased capacity to differentiate as well as activate phosphorylation of the retinoblastoma protein. Additionally, these cells acquire an impaired p53-mediated DNA-damage response as a late event in immortalization. We conclude that bHLH proteins play a pivotal role in regulating normal keratinocyte growth and differentiation, which can be disrupted by the immortalizing functions of Id-1 through activation of telomerase activity and inactivation of the retinoblastoma protein.

Original languageEnglish (US)
Pages (from-to)9637-9641
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume96
Issue number17
DOIs
StatePublished - Aug 17 1999
Externally publishedYes

Keywords

  • Differentiation
  • Senescence
  • Telomerase
  • Transcription

ASJC Scopus subject areas

  • Genetics
  • General

Fingerprint

Dive into the research topics of 'Immortalization of primary human keratinocytes by the helix-loop-helix protein, Id-1'. Together they form a unique fingerprint.

Cite this