Ca2+ and BMP-6 Signaling Regulate E2F during Epidermal Keratinocyte Differentiation*

@article{Dsouza2001Ca2AB,
  title={Ca2+ and BMP-6 Signaling Regulate E2F during Epidermal Keratinocyte Differentiation*},
  author={Sudhir J. A. D'souza and Agnieszka Katarzyna Pająk and Kim Balazsi and Lina Dagnino},
  journal={The Journal of Biological Chemistry},
  year={2001},
  volume={276},
  pages={23531 - 23538}
}
The epidermis consists of a squamous epithelium continuously replenished by committed stem cells, which can either self-renew or differentiate. We demonstrated previously that E2F genes are differentially expressed in developing epidermis (Dagnino, L., Fry, C. J., Bartley, S. M., Farnham, P., Gallie, B. L., and Phillips, R. A. (1997) Cell Growth Differ. 8, 553–563). Thus, we hypothesized that various E2F proteins likely play distinct growth regulatory roles in the undifferentiated stem cells… 

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References

SHOWING 1-10 OF 65 REFERENCES

Expression patterns of the E2F family of transcription factors during murine epithelial development.

Positive regulation of E2F forms occurs during murine epithelial development, irrespective of the ectodermal or endodermal origin of such epithelia, and this suggests that E 2F-2 and E2f-4 may participate in maintaining epithelial cells in a proliferative, undifferentiated phenotype.

Differential expression and functionally co-operative roles for the retinoblastoma family of proteins in epidermal differentiation

The results indicate that the members of the pRb family play specific, yet co-ordinated roles during epidermal differentiation, and that the ordered progression along the different stages of this process results from the effects of different combinations of these proteins.

E2F-1 induces proliferation-specific genes and suppresses squamous differentiation-specific genes in human epidermal keratinocytes

It is shown that E2F-1 mRNA expression is increased in primary squamous cell carcinomas of the skin relative to normal epidermis, indicating that targeted disruption of E2f-1 activity may have therapeutic potential for the treatment of squamous carcinomas.

Signal transduction pathways controlling the switch between keratinocyte growth and differentiation.

  • G. Dotto
  • Biology
    Critical reviews in oral biology and medicine : an official publication of the American Association of Oral Biologists
  • 1999
This review focuses on the significant progress that has been made over the last few years in understanding of the specific signals that trigger keratinocytes differentiation, the underlying signaling pathways, and how they impinge on specific transcription and cell-cycle control mechanisms associated with the onset of keratinocyte differentiation.

Expression and growth inhibitory effect of decapentaplegic Vg-related protein 6: evidence for a regulatory role in keratinocyte differentiation.

Expression of DVR-6 in primary mouse keratinocytes before differentiation resulted in the secretion of prepro and processed (pro region) forms in the conditioned medium and a dramatic inhibition of cell growth, suggesting that inhibition ofcell growth by DVR -6 may be a primary step in keratinocyte differentiation.

Alterations in cyclin‐dependent kinase 2 function during differentiation of primary human keratinocytes

The model that multiple CKIs participate in linking cellular proliferation and differentiation in human keratinocytes by specific modulation of cdk2 activity is supported.

The absence of p21Cip1/WAF1 alters keratinocyte growth and differentiation and promotes ras-tumor progression.

The results reveal a so far undetected role of p 21 in tumor suppression, demonstrate that this function is specific as it cannot be attributed to the closely related p27 molecule, and point to an essential involvement of p21 in terminal differentiation control, which may account for its role in tumors suppression.

Coordinated changes in cell cycle machinery occur during keratinocyte terminal differentiation

The previously described v-Ha-ras block of keratinocyte differentiation correlates with altered regulation of both cyclin D1 and cdk2 suggesting that these genes may play a role in the Ha-ras transformation of a keratinocytes.
...