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Immortalization of primary human keratinocytes by the helix-loop-helix protein, Id-1
- Source :
- Proceedings of the National Academy of Sciences of the United States. August 17, 1999, Vol. 96 Issue 17, p9637, 5 p.
- Publication Year :
- 1999
-
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 within 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.
- Subjects :
- Keratinocytes -- Research
DNA binding proteins -- Research
Science and technology
Subjects
Details
- ISSN :
- 00278424
- Volume :
- 96
- Issue :
- 17
- Database :
- Gale General OneFile
- Journal :
- Proceedings of the National Academy of Sciences of the United States
- Publication Type :
- Academic Journal
- Accession number :
- edsgcl.55726806