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

被引:18
作者
Bhatia, Neehar [1 ]
Demmer, Tara A. [2 ]
Sharma, Alok K. [3 ]
Elcheva, Irina [4 ]
Spiegelman, Vladimir S. [1 ]
机构
[1] Univ Wisconsin, Sch Med & Publ Hlth, Dept Dermatol, Madison, WI 53706 USA
[2] Des Moines Univ, Des Moines, IA USA
[3] Covance Labs Inc, Madison, WI USA
[4] WiCell Res Inst Inc, Madison, WI USA
关键词
Skin Cancer; UVB; beta-TrCP; beta-TrCP(Delta F)transgenic mice; IL-6; Inflammation; NF-KAPPA-B; ORNITHINE-DECARBOXYLASE; INDUCED IMMUNOSUPPRESSION; CANCER; INTERLEUKIN-6; MICE; DEGRADATION; EPIDERMIS; CELLS; SUPPRESSION;
D O I
10.1016/j.abb.2010.12.023
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 beta-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 (beta-TrCP) is often found in cancer cell lines and primary tumors. We have previously demonstrated that beta-TrCP2 is over-expressed in chemically induced mouse skin tumors [1]. Various cellular stress stimuli, including UVB, induce an increase in beta-TrCP1 mRNA and protein levels in human cells [2]. We have previously shown that inhibition of beta-TrCP function, by induction of dominant negative beta-TrCP2 (beta-TrCP2(Delta F)), 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 beta-TrCP2 in epidermis with the Keratin 5 promoter (K5-rTA x TRE-HA-beta-TrCP Delta F). Here we report that inhibition of beta-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 beta-TrCP may be an essential player in UVB induced responses in skin and can be a potential therapeutic target for skin cancer. Published by Elsevier Inc.
引用
收藏
页码:178 / 184
页数:7
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