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Candidate tumor suppressor LUCA-15/RBM5/H37 modulates expression of apoptosis and cell cycle genes.

Abstract
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.
AuthorsMirna Mourtada-Maarabouni, Jennifer Keen, Jeremy Clark, Colin S Cooper, Gwyn T Williams
JournalExperimental cell research (Exp Cell Res) Vol. 312 Issue 10 Pg. 1745-52 (Jun 10 2006) ISSN: 0014-4827 [Print] United States
PMID16546166 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • MAS1 protein, human
  • Proto-Oncogene Mas
  • RBM5 protein, human
  • RNA-Binding Proteins
  • Tumor Suppressor Proteins
Topics
  • Animals
  • Apoptosis (physiology)
  • Cell Cycle (physiology)
  • Cell Cycle Proteins (genetics, metabolism)
  • Cell Line, Tumor
  • DNA-Binding Proteins (genetics, metabolism)
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Genes, Tumor Suppressor
  • Genes, cdc
  • Humans
  • Molecular Sequence Data
  • Oligonucleotide Array Sequence Analysis
  • Proto-Oncogene Mas
  • RNA-Binding Proteins (genetics, metabolism)
  • Tumor Suppressor Proteins (genetics, metabolism)

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