DOI: 10.1073/pnas.082123999. Negative regulation of cell growth and differentiation by TSG101 through association with p21 <sup>Cip1/WAF1</sup>

Negative regulation of cell growth and differentiation by TSG101 through association with p21 Cip1/WAF1

10.1073/pnas.082123999

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

TSG101 was discovered in a screen for tumor susceptibility genes and has since been shown to have a multiplicity of biological effects. However, the basis for TSG101's ability to regulate cell growth has not been elucidated. We report here that the TSG101 protein binds to the cyclin/cyclin-dependent kinase (CDK) inhibitor (CKI) p21 Cip1/WAF1 and increases stability of the p21 protein in HEK293F cells and differentiating primary keratinocytes, suppressing differentiation in a p21-dependent manner. In proliferating keratinocytes where the p21 protein is relatively stable, TSG101 does not affect the stability or expression of p21 but shows p21-dependent recruitment to cyclin/CDK complexes, inhibits cyclin/CDK activity, and causes strong growth suppression to a much greater extent in p21+/+ than in p21−/− cells. Conversely, suppression of endogenous TSG101 expression by an antisense TSG101 cDNA causes doubling of the fraction of keratinocytes in the S phase of the cell cycle as occurs during p21 deficiency. Our results indicate that TSG101 has a direct role in the control of growth and differentiation in primary epithelial cells, and that p21 is an important mediator of these TSG101 functions.

Bibliography

Oh, H., Mammucari, C., Nenci, A., Cabodi, S., Cohen, S. N., & Dotto, G. P. (2002). Negative regulation of cell growth and differentiation by TSG101 through association with p21 Cip1/WAF1. Proceedings of the National Academy of Sciences, 99(8), 5430â5435.

Authors 6

Hyesun Oh (first)
Cristina Mammucari (additional)
Arianna Nenci (additional)
Sara Cabodi (additional)
Stanley N. Cohen (additional)
G. Paolo Dotto (additional)

References 35 Referenced 45

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Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:45 a.m.)
Deposited	3 years, 4 months ago (April 12, 2022, 6:25 p.m.)
Indexed	1 month, 3 weeks ago (July 11, 2025, 6:23 a.m.)
Issued	23 years, 4 months ago (April 9, 2002)
Published	23 years, 4 months ago (April 9, 2002)
Published Online	23 years, 4 months ago (April 9, 2002)
Published Print	23 years, 4 months ago (April 16, 2002)

Funders 0

None

BibTeX

@article{Oh_2002, title={Negative regulation of cell growth and differentiation by TSG101 through association with p21 Cip1/WAF1}, volume={99}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.082123999}, DOI={10.1073/pnas.082123999}, number={8}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Oh, Hyesun and Mammucari, Cristina and Nenci, Arianna and Cabodi, Sara and Cohen, Stanley N. and Dotto, G. Paolo}, year={2002}, month=apr, pages={5430–5435} }

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  "abstract": "<jats:p>\n            TSG101 was discovered in a screen for tumor susceptibility genes and has since been shown to have a multiplicity of biological effects. However, the basis for TSG101's ability to regulate cell growth has not been elucidated. We report here that the TSG101 protein binds to the cyclin/cyclin-dependent kinase (CDK) inhibitor (CKI) p21\n            <jats:sup>Cip1/WAF1</jats:sup>\n            and increases stability of the p21 protein in HEK293F cells and differentiating primary keratinocytes, suppressing differentiation in a p21-dependent manner. In proliferating keratinocytes where the p21 protein is relatively stable, TSG101 does not affect the stability or expression of p21 but shows p21-dependent recruitment to cyclin/CDK complexes, inhibits cyclin/CDK activity, and causes strong growth suppression to a much greater extent in p21+/+ than in p21\u2212/\u2212 cells. Conversely, suppression of endogenous TSG101 expression by an antisense TSG101 cDNA causes doubling of the fraction of keratinocytes in the S phase of the cell cycle as occurs during p21 deficiency. Our results indicate that TSG101 has a direct role in the control of growth and differentiation in primary epithelial cells, and that p21 is an important mediator of these TSG101 functions.\n          </jats:p>",
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