Search for UV-Responsive Genes in Human Cells by Differential mRNA Display: Involvement of Human Ras-Related GTP-Binding Protein, Rheb, in UV Susceptibility

• Published in: Biochemical and biophysical research communications 2000-08, Vol.274 (3), p.859-864
• Main Authors: Kita, Kazuko, Wu, Yu-Ping, Sugaya, Shigeru, Moriya, Tetsuhiro, Nomura, Jun, Takahashi, Shunji, Yamamori, Hideo, Nakajima, Nobuyuki, Suzuki, Nobuo
• Format: Article
• Language: English
• Subjects: Cell Death - genetics; Cell Death - radiation effects; Gene Expression Profiling; Gene Expression Regulation - radiation effects; Gene Library; Genes, ras; Humans; Monomeric GTP-Binding Proteins - genetics; Neuropeptides - genetics; Ras Homolog Enriched in Brain Protein; Rheb protein; RNA, Messenger - analysis; RNA, Messenger - genetics; Ultraviolet Rays
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.2000.3220

The search for genes responsible for the sensitivity of human cells to cell-killing effects of UV is an important area of biological research. To identify candidate genes responsible for UV sensitization, levels of mRNA expression were compared between UV-sensitive RSa cells and UV-resistant variant UVr-1 cells, using a differential display method and Northern blot analysis. Messenger RNA expression levels of human Ras homologue enriched in brain (Rheb) and/or a Rheb-like gene were up-regulated and slightly decreased in UV-irradiated RSa and UVr-1 cells, compared to in mock-irradiated cells, respectively. RSa and UVr-1 cells, both of which were treated with antisense oligonucleotides for Rheb RNA, exhibited an increased resistance to UV cell-killing. It remains unclear why UVr-1 cells are resistant to UV yet express Rheb mRNA at high levels. However, the results of antisense experiments together with the up-regulation in UV-irradiated RSa cells, suggest that Rheb is involved in the UV sensitization of both cells to UV cell-killing.