Stability and function of mammalian lethal giant larvae-1 oncoprotein are regulated by the scaffolding protein RanBPM.

Abstract	The evolutionarily conserved lethal giant larvae (Lgl) tumor suppressor gene has an essential role in establishing apical-basal cell polarity, cell proliferation, differentiation, and tissue organization. However, the precise molecular mechanism by which the Lgl carries out its function remains obscure. In the current study, we have identified Ran-binding protein M (RanBPM) as a novel binding partner of Mgl-1, a mammalian homolog of Drosophila tumor suppressor protein lethal (2) giant larvae (L(2)gl) by yeast two-hybrid screening. RanBPM seems to act as a scaffolding protein with a modulatory function with respect to Mgl-1. The Mgl-1 and RanBPM association was confirmed by co-immunoprecipitation and GST pull-down experiments. Additionally, expression of RanBPM resulted in inhibition of Mgl-1 degradation, and thereby extended the half-life of Mgl-1. Furthermore, the ability of Mgl-1 activity in cell migration and colony formation assay was enhanced by RanBPM. Taken together, our findings reveal that RanBPM plays a novel role in regulating Mgl-1 stability and contributes to its biological function as a tumor suppressor.
Authors	Bharathi Suresh, Suresh Ramakrishna, Yong-Soo Kim, Sun-Myoung Kim, Myung-Sun Kim, Kwang-Hyun Baek
Journal	The Journal of biological chemistry (J Biol Chem) Vol. 285 Issue 46 Pg. 35340-9 (Nov 12 2010) ISSN: 1083-351X [Electronic] United States
PMID	20829363 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Adaptor Proteins, Signal Transducing Cytoskeletal Proteins Homeodomain Proteins Llgl1 protein, mouse Nuclear Proteins Ran binding protein 9 Tumor Suppressor Proteins
Topics	Adaptor Proteins, Signal Transducing (genetics, metabolism) Animals Binding Sites Blotting, Western Cell Line Cell Movement Cell Proliferation Cytoskeletal Proteins (genetics, metabolism) HEK293 Cells HeLa Cells Homeodomain Proteins (genetics, metabolism) Humans Immunoprecipitation Nuclear Proteins (genetics, metabolism) Protein Binding Protein Stability Transfection Tumor Suppressor Proteins (genetics, metabolism) Two-Hybrid System Techniques Ubiquitination

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