Abstract
The FEZ1/LZTS1 gene maps to chromosome 8p22, a region that is frequently deleted in human tumors. Alterations in FEZ1/LZTS1 expression have been observed in esophageal, breast, and prostate cancers. Here, we show that introduction of FEZ1/LZTS1 into Fez1/Lzts1-negative cancer cells results in suppression of tumorigenicity and reduced cell growth with accumulation of cells at late S-G(2)/M stage of the cell cycle. Fez1/Lzts1 protein is hyperphosphorylated by cAMP-dependent kinase during cell-cycle progression. We found that Fez1/Lzts1 is associated with microtubule components and interacts with p34(cdc2) at late S-G(2)/M stage in vivo. Present data show that FEZ1/LZTS1 inhibits cancer cell growth through regulation of mitosis, and that its alterations result in abnormal cell growth.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adaptor Proteins, Signal Transducing
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CDC2 Protein Kinase / metabolism
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Cell Cycle / genetics
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Cell Division / genetics
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Chromosomes, Human, Pair 8 / genetics*
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DNA-Binding Proteins / genetics*
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DNA-Binding Proteins / metabolism
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Female
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Genes, Tumor Suppressor*
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Humans
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Male
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Microtubules / metabolism
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Mitosis / genetics
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Neoplasms / genetics*
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Neoplasms / metabolism
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Neoplasms / pathology*
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Nerve Tissue Proteins
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Peptide Elongation Factor 1 / metabolism
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Phosphorylation
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Protein Binding
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Transfection
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Tumor Cells, Cultured
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Tumor Suppressor Proteins*
Substances
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Adaptor Proteins, Signal Transducing
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DNA-Binding Proteins
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FEZ1 protein, human
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LZTS1 protein, human
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Nerve Tissue Proteins
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Peptide Elongation Factor 1
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Tumor Suppressor Proteins
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CDC2 Protein Kinase