Abstract
Appropriate cell number and organ size in a multicellular organism are determined by coordinated cell growth, proliferation, and apoptosis. Disruption of these processes can cause cancer. Recent studies have identified the Large tumor suppressor (Lats)/Warts (Wts) protein kinase as a key component of a pathway that controls the coordination between cell proliferation and apoptosis. Here we describe growth inhibitory functions for a Mob superfamily protein, termed Mats (Mob as tumor suppressor), in Drosophila. Loss of Mats function results in increased cell proliferation, defective apoptosis, and induction of tissue overgrowth. We show that mats and wts function in a common pathway. Mats physically associates with Wts to stimulate the catalytic activity of the Wts kinase. A human Mats ortholog (Mats1) can rescue the lethality associated with loss of Mats function in Drosophila. As Mats1 is mutated in human tumors, Mats-mediated growth inhibition and tumor suppression is likely conserved in humans.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
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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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Animals
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Apoptosis / physiology*
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Cell Line
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Cell Proliferation*
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Cell Transformation, Neoplastic / genetics
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Cell Transformation, Neoplastic / metabolism*
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Conserved Sequence
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DNA, Complementary / analysis
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DNA, Complementary / genetics
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Drosophila
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Drosophila Proteins / genetics
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Drosophila Proteins / isolation & purification
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Drosophila Proteins / metabolism*
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Evolution, Molecular
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Gene Expression Regulation, Developmental / genetics
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Humans
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Membrane Proteins / genetics
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Membrane Proteins / metabolism
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Mice
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Microscopy, Electron, Scanning
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Molecular Sequence Data
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Mutation / genetics
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Neoplasms / genetics
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Neoplasms / metabolism*
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism
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Protein Kinases / metabolism*
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Sequence Homology, Amino Acid
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Sequence Homology, Nucleic Acid
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Transferases (Other Substituted Phosphate Groups)
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Tumor Suppressor Proteins / genetics
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Tumor Suppressor Proteins / isolation & purification
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Tumor Suppressor Proteins / metabolism*
Substances
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Adaptor Proteins, Signal Transducing
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DNA, Complementary
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Drosophila Proteins
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MOB1A protein, human
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Mats protein, Drosophila
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Membrane Proteins
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Nerve Tissue Proteins
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Tumor Suppressor Proteins
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Protein Kinases
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wts protein, Drosophila
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SGMS1 protein, human
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Transferases (Other Substituted Phosphate Groups)