Role of β-TrCP ubiquitin ligase receptor in UVB mediated responses in skin

Neehar Bhatia, Tara A. Demmer, Alok K. Sharma, Irina Elcheva, Vladimir Spiegelman

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Skin cancers are the most common cancers in the United States. Exposure to UVB radiation is a major risk factor for skin cancer induction. SCF β-TrCP E3 ubiquitin ligase has been found to be involved in cell cycle, cell proliferation and transformation. Aberrant up-regulation of beta-transducin repeats-containing proteins (β-TrCP) is often found in cancer cell lines and primary tumors. We have previously demonstrated that β-TrCP2 is over-expressed in chemically induced mouse skin tumors [1]. Various cellular stress stimuli, including UVB, induce an increase in β-TrCP1 mRNA and protein levels in human cells [2]. We have previously shown that inhibition of β-TrCP function, by induction of dominant negative β-TrCP2 (β-TrCP2 ΔF), in vitro in hTERT immortalized normal keratinocytes, results in increase in UVB induced apoptosis [3]. We have generated transgenic mice with inducible, selective expression of dominant negative β-TrCP2 in epidermis with the Keratin 5 promoter (K5-rTA × TRE-HA-β-TrCP ΔF). Here we report that inhibition of β-TrCP function in mouse epidermis results in decrease in UVB-induced edema, hyperplasia, and inflammatory response and increment in UVB-induced apoptosis in skin. Our results suggest that β-TrCP may be an essential player in UVB induced responses in skin and can be a potential therapeutic target for skin cancer.

Original languageEnglish (US)
Pages (from-to)178-184
Number of pages7
JournalArchives of Biochemistry and Biophysics
Volume508
Issue number2
DOIs
StatePublished - Apr 15 2011

Fingerprint

Skin Neoplasms
Ligases
Ubiquitin
Skin
Epidermis
beta-Transducin Repeat-Containing Proteins
Keratin-5
Apoptosis
Neoplasms
Ubiquitin-Protein Ligases
Cells
Tumor Cell Line
Keratinocytes
Transgenic Mice
Hyperplasia
Tumors
Edema
Cell Cycle
Up-Regulation
Cell Proliferation

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology

Cite this

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title = "Role of β-TrCP ubiquitin ligase receptor in UVB mediated responses in skin",
abstract = "Skin cancers are the most common cancers in the United States. Exposure to UVB radiation is a major risk factor for skin cancer induction. SCF β-TrCP E3 ubiquitin ligase has been found to be involved in cell cycle, cell proliferation and transformation. Aberrant up-regulation of beta-transducin repeats-containing proteins (β-TrCP) is often found in cancer cell lines and primary tumors. We have previously demonstrated that β-TrCP2 is over-expressed in chemically induced mouse skin tumors [1]. Various cellular stress stimuli, including UVB, induce an increase in β-TrCP1 mRNA and protein levels in human cells [2]. We have previously shown that inhibition of β-TrCP function, by induction of dominant negative β-TrCP2 (β-TrCP2 ΔF), in vitro in hTERT immortalized normal keratinocytes, results in increase in UVB induced apoptosis [3]. We have generated transgenic mice with inducible, selective expression of dominant negative β-TrCP2 in epidermis with the Keratin 5 promoter (K5-rTA × TRE-HA-β-TrCP ΔF). Here we report that inhibition of β-TrCP function in mouse epidermis results in decrease in UVB-induced edema, hyperplasia, and inflammatory response and increment in UVB-induced apoptosis in skin. Our results suggest that β-TrCP may be an essential player in UVB induced responses in skin and can be a potential therapeutic target for skin cancer.",
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Role of β-TrCP ubiquitin ligase receptor in UVB mediated responses in skin. / Bhatia, Neehar; Demmer, Tara A.; Sharma, Alok K.; Elcheva, Irina; Spiegelman, Vladimir.

In: Archives of Biochemistry and Biophysics, Vol. 508, No. 2, 15.04.2011, p. 178-184.

Research output: Contribution to journalArticle

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