c-Myc stimulates cell invasion by inhibiting FBX8 function.
c-Myc is a cellular onco-protein and a transcriptional activator important for cell growth, cell division, and tumorigenesis. Despite all that is known of its function, the mechanism of how c-Myc contributes to tumorigenesis is unclear. To gain insight into the mechanism through which c-Myc protein exerts its oncogenic activity, we performed large-scale, tandem repeat affinity purification and identified the F box only protein 8 (FBX8), an F-box- and Sec7 domain-containing protein, as a novel Myc-binding protein. The c-Myc/FBX8 interaction was mediated by the c-Myc box II (MBII) region. We also confirmed that Myc protein overexpression in 293T cells affected FBX8 cellular translocation and led to recovery from FBX8-mediated inhibition of ADP-ribosylation factor 6 (ARF6) function during cell invasion. Together, these results suggest that FBX8 is a novel c-Myc binding protein and that c-Myc induces cell invasive activity through the inhibition of FBX8 effects on ARF6 function during cell invasion.
Cho
Hyun Jung
HJ
Department of Biological Sciences, Sungkyunkwan University, Suwon, 440-746, Korea.
Oh
Yun Jeong
YJ
Kwon
Junhye
J
Kwon
Jae Young
JY
Kim
Kyung-Soo
KS
Kim
Hongtae
H
D000089982:ADP-Ribosylation Factor 6; D020727:ADP-Ribosylation Factors / Q000235:genetics / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002455:Cell Division; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D044783:F-Box Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008856:Microscopy, Fluorescence; D009361:Neoplasm Invasiveness / Q000235:genetics*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D020080:Tandem Repeat Sequences; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D054875:Ubiquitination
D000089982:ADP-Ribosylation Factor 6; D015815:Cell Adhesion Molecules; D044783:F-Box Proteins; C555947:FBXO8 protein, human; D016271:Proto-Oncogene Proteins c-myc; D014157:Transcription Factors; D020727:ADP-Ribosylation Factors; C000715348:ARF6 protein, human