LNX (Ligand of Numb-protein X) interacts with RhoC, both of which regulate AP-1-mediated transcriptional activation.
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.
Zheng
Dan
D
State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, 200433 Shanghai, People's Republic of China.
Sun
Yaqiong
Y
Gu
Shaohua
S
Ji
Chaoneng
C
Zhao
Wei
W
Xie
Yi
Y
Mao
Yumin
Y
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
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
Cell. 1994 Feb 11;76(3):477-91
8313469
Breast Cancer Res Treat. 2004 Mar;84(1):13-9
14999150
Curr Opin Neurobiol. 1997 Feb;7(1):21-8
9039790
J Cell Sci. 2004 Dec 1;117(Pt 25):5965-73
15564374
Int J Biochem Cell Biol. 2005 Nov;37(11):2273-83
16002321
Biochem Biophys Res Commun. 2007 Mar 16;354(3):686-92
17257582
Neuron. 1996 Jul;17(1):27-41
8755476
Exp Cell Res. 2004 Nov 15;301(1):43-9
15501444
Cancer Immunol Immunother. 2008 Dec;57(12):1871-8
18415097
Neuron. 1996 Jul;17(1):21-6
8755475
Trends Neurosci. 1995 Sep;18(9):379-83
7482802
Cell. 1989 Jul 28;58(2):349-60
2752427
Science. 1997 Dec 19;278(5346):2075-80
9405336
J Biol Chem. 1998 Apr 10;273(15):9179-87
9535908
J Biol Chem. 2003 Feb 28;278(9):7439-44
12468544
Nature. 2002 Dec 12;420(6916):629-35
12478284
Neuron. 1995 Oct;15(4):761-8
7576626
Oncogene. 2006 Aug 24;25(37):5071-84
16832352
Curr Opin Cell Biol. 1997 Feb;9(1):86-92
9013670
Nat Rev Cancer. 2002 Feb;2(2):133-42
12635176
J Biol Chem. 2004 May 14;279(20):20807-15
14990566
J Cell Sci. 2001 Sep;114(Pt 18):3219-31
11591811
Mol Cell Neurosci. 2001 Nov;18(5):525-40
11922143
FEBS Lett. 2007 Oct 30;581(26):5131-6
17936276
Bioessays. 1997 Jun;19(6):469-79
9204764
EMBO J. 2002 Jan 15;21(1-2):93-102
11782429
Development. 1995 Nov;121(11):3489-94
8582263
Genes Dev. 2005 Sep 1;19(17):1974-9
16107613