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Skp2 deficiency inhibits chemical skin tumorigenesis independent of p27(Kip1) accumulation.

Publication ,  Journal Article
Sistrunk, C; Kim, SH; Wang, X; Lee, SH; Kim, Y; Macias, E; Rodriguez-Puebla, ML
Published in: Am J Pathol
May 2013

S-phase kinase-associated protein 2 (Skp2) functions as the receptor component of the Skp-Cullin-F-box complex and is implicated in the degradation of several cell cycle regulators, such as p21(Cip1), p27(Kip1), p57(Kip2), and cyclin E. Numerous studies in human and experimental tumors have demonstrated low p27(Kip1) levels and elevated Skp2 expression. However, a direct association between the inverse correlation of Skp2 and p27(Kip1) with tumorigenesis has not been demonstrated. Herein, we provide evidence that skin tumorigenesis is inhibited in Skp2(-/-) mice. An analysis of mouse keratinocytes indicates that increased p27(Kip1) levels in Skp2(-/-) epidermis cause reduced cell proliferation that is alleviated in the epidermis from Skp2(-/-)/p27(-/-) compound mice. In contrast, we establish that a p27(Kip1) deficiency does not overturn the reduced skin tumorigenesis experienced by Skp2(-/-) mice. In addition, Skp2(-/-) epidermis exhibits an accumulation of p53-cofactor CBP/p300 that is associated with elevated apoptosis in hair follicles and decreased skin tumorigenesis. We conclude that p27(Kip1) accumulation is responsible for the hypoplasia observed in normal tissues of Skp2(-/-) mice but does not have a preponderant function in reducing skin tumorigenesis.

Duke Scholars

Published In

Am J Pathol

DOI

EISSN

1525-2191

Publication Date

May 2013

Volume

182

Issue

5

Start / End Page

1854 / 1864

Location

United States

Related Subject Headings

  • Tumor Suppressor Protein p53
  • Skin Neoplasms
  • S-Phase Kinase-Associated Proteins
  • Pathology
  • Papilloma
  • Mice, Inbred C57BL
  • Mice
  • Kinetics
  • Humans
  • Gene Deletion
 

Citation

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ICMJE
MLA
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Sistrunk, C., Kim, S. H., Wang, X., Lee, S. H., Kim, Y., Macias, E., & Rodriguez-Puebla, M. L. (2013). Skp2 deficiency inhibits chemical skin tumorigenesis independent of p27(Kip1) accumulation. Am J Pathol, 182(5), 1854–1864. https://doi.org/10.1016/j.ajpath.2013.01.016
Sistrunk, Christopher, Sun Hye Kim, Xian Wang, Sung Hyun Lee, Yongbaek Kim, Everardo Macias, and Marcelo L. Rodriguez-Puebla. “Skp2 deficiency inhibits chemical skin tumorigenesis independent of p27(Kip1) accumulation.Am J Pathol 182, no. 5 (May 2013): 1854–64. https://doi.org/10.1016/j.ajpath.2013.01.016.
Sistrunk C, Kim SH, Wang X, Lee SH, Kim Y, Macias E, et al. Skp2 deficiency inhibits chemical skin tumorigenesis independent of p27(Kip1) accumulation. Am J Pathol. 2013 May;182(5):1854–64.
Sistrunk, Christopher, et al. “Skp2 deficiency inhibits chemical skin tumorigenesis independent of p27(Kip1) accumulation.Am J Pathol, vol. 182, no. 5, May 2013, pp. 1854–64. Pubmed, doi:10.1016/j.ajpath.2013.01.016.
Sistrunk C, Kim SH, Wang X, Lee SH, Kim Y, Macias E, Rodriguez-Puebla ML. Skp2 deficiency inhibits chemical skin tumorigenesis independent of p27(Kip1) accumulation. Am J Pathol. 2013 May;182(5):1854–1864.
Journal cover image

Published In

Am J Pathol

DOI

EISSN

1525-2191

Publication Date

May 2013

Volume

182

Issue

5

Start / End Page

1854 / 1864

Location

United States

Related Subject Headings

  • Tumor Suppressor Protein p53
  • Skin Neoplasms
  • S-Phase Kinase-Associated Proteins
  • Pathology
  • Papilloma
  • Mice, Inbred C57BL
  • Mice
  • Kinetics
  • Humans
  • Gene Deletion