Ribosomal protein L4 positively regulates activity of a c-myb proto-oncogene product.
The c-myb proto-oncogene product (c-Myb) induces transcription of a group of target genes involved in the G1/S transition and in anti-apoptosis. The level of c-Myb is negatively regulated by the Wnt signal, but it remains obscure how c-Myb activity is positively regulated. We have found that ribosomal protein L4 (RPL4) binds to the DNA-binding domain of c-Myb. Co-immunoprecipitation experiments also indicated that RPL4 interacts with c-Myb. When c-Myb was overexpressed in CV-1 cells, significant amounts of RPL4 moved to the nucleoplasm from the nucleolus. RPL4 stimulated the c-Myb-dependent expression of a c-myc-luciferase reporter construct. Chromatin immunoprecipitation assays indicated that RPL4 binds to the 5'-regulatory region of the c-myc gene via c-Myb. Serum starvation and 2-deoxyglucose treatment of NIH3T3 cells induced the movement of RPL4 from the nucleoplasm to the nucleolus. Furthermore, c-myc mRNA levels were reduced by either serum starvation or 2-deoxyglucose treatment, and the degree of reduction in the c-myc mRNA level was correlated with the RPL4 level. These results suggest that growth factor and nutritional signals positively regulate c-Myb activity via its interaction with RPL4. Thus, RPL4 plays an important role in c-myc expression by interacting with c-Myb in response to growth factor and nutritional signals.
Egoh
Ayako
A
Laboratory of Molecular Genetics, RIKEN Tsukuba Institute, 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan.
Nosuke Kanesashi
Shin
S
Kanei-Ishii
Chie
C
Nomura
Teruaki
T
Ishii
Shunsuke
S
D000818:Animals; D002460:Cell Line; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D000090063:Proto-Oncogene Mas; D020598:Proto-Oncogene Proteins c-myb / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism*
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D020598:Proto-Oncogene Proteins c-myb; D012333:RNA, Messenger; D012269:Ribosomal Proteins; C056368:ribosomal protein L4