Candidate tumor suppressor LUCA-15/RBM5/H37 modulates expression of apoptosis and cell cycle genes.
RBM5 (RNA-binding motif protein 5/LUCA-15/H37) is encoded at the lung cancer tumor suppressor locus 3p21.3 and itself has several important characteristics of a tumor suppressor, including both potentiation of apoptosis and inhibition of the cell cycle. Here, we report the effects of both upregulation and downregulation of LUCA-15/RBM5 on gene expression monitored using cDNA microarrays. Many of the genes modulated by LUCA-15/RBM5 are involved in the control of apoptosis, the cell cycle, or both. These effects were confirmed for the most significant genes using real-time RT-PCR and/or Western blotting. In particular, LUCA-15/RBM5 increased the expression of Stat5b and BMP5 and decreased the expression of AIB1 (Amplified In Breast Cancer 1), proto-oncogene Pim-1, caspase antagonist BIRC3 (cIAP-2, MIHC), and CDK2 (cyclin-dependent kinase 2). These effects on multiple genes controlling both apoptosis and proliferation are in line with the functional effects of LUCA-15/RBM5 and indicate that it plays a central role in regulating cell fate consistent with its tumor suppressor activity.
School of Life Sciences, Keele University, Keele ST5 5BG, UK. bia19@biol.keele.ac.uk
Mirna
M
Mourtada-Maarabouni
Jennifer
J
Keen
Jeremy
J
Clark
Colin S
CS
Cooper
Gwyn T
GT
Williams
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D016147:Genes, Tumor Suppressor; D018816:Genes, cdc; D006801:Humans; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D000090063:Proto-Oncogene Mas; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; C473448:RBM5 protein, human; D016601:RNA-Binding Proteins; D025521:Tumor Suppressor Proteins