| First Author | Bhatia N | Year | 2011 |
| Journal | Arch Biochem Biophys | Volume | 508 |
| Issue | 2 | Pages | 178-84 |
| PubMed ID | 21187057 | Mgi Jnum | J:171643 |
| Mgi Id | MGI:4950661 | Doi | 10.1016/j.abb.2010.12.023 |
| Citation | Bhatia N, et al. (2011) Role of beta-TrCP ubiquitin ligase receptor in UVB mediated responses in skin. Arch Biochem Biophys 508(2):178-84 |
| abstractText | 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. Various cellular stress stimuli, including UVB, induce an increase in beta-TrCP1 mRNA and protein levels in human cells. We have previously shown that inhibition of beta-TrCP function, by induction of dominant negative beta-TrCP2 (beta-TrCP2(DeltaF)), in vitro in hTERT immortalized normal keratinocytes, results in increase in UVB induced apoptosis. 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(DeltaF)). 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. |
