title: LNX (Ligand of Numb-protein X) interacts with RhoC, both of which regulate AP-1-mediated transcriptional activation.
abstract: LNX (Ligand of Numb-protein X) was originally isolated as a binding partner to the cell-fate Determinant Numb during development, and then identified to act as a RING finger-type E3 ubiquitin ligase for the ubiquitylation and degradation of Numb. LNX contains 4 PDZ domains which are proved to play a central role in organizing diverse cell signaling assemblies. A yeast two-hybrid screening was used to identify LNX as a potential binding partner for RhoC. RhoC, a member of the Ras family of small GTPases, promotes reorganization of the actin cytoskeleton and regulation of cell shape, attachment, and motility. The interaction between LNX and RhoC in mammalian cells was identified by co-immunoprecipitation assays, and the efficient binding required the first PDZ domain of LNX. LNX and RhoC were further colocalized with each other in mammalian cells, in which RhoC changed its sublocalization from cytoplasm to nucleus when co-transferred with LNX. Furthermore, co-expression of RhoC reduced the transcriptional activity of AP-1, which was up-regulated by over-expression of LNX alone. These results suggest that LNX and RhoC might be part of a larger protein complex that would have important functions in signaling transduction about regulating the transcriptional activities of AP-1.
authors.affiliation: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, 200433 Shanghai, People's Republic of China.
authors.forename: Dan
authors.initials: D
authors.lastname: Zheng
authors.forename: Yaqiong
authors.initials: Y
authors.lastname: Sun
authors.forename: Shaohua
authors.initials: S
authors.lastname: Gu
authors.forename: Chaoneng
authors.initials: C
authors.lastname: Ji
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.forename: Yi
authors.initials: Y
authors.lastname: Xie
authors.forename: Yumin
authors.initials: Y
authors.lastname: Mao
mesh_terms: D002460:Cell Line; D005453:Fluorescence; D006801:Humans; D047468:Immunoprecipitation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry / Q000378:metabolism*; D020741:rho GTP-Binding Proteins / Q000378:metabolism*; D000075024:rhoC GTP-Binding Protein
chemical_list: D018808:Transcription Factor AP-1; C484733:LNX1 protein, human; D044767:Ubiquitin-Protein Ligases; C066690:RHOC protein, human; D020741:rho GTP-Binding Proteins; D000075024:rhoC GTP-Binding Protein
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