Identification of semaphorin3B as a direct target of p53.
A cDNA microarray analysis indicated that Semaphorin3B (Sema3B), a gene whose product is involved in axon guidance and axonal repulsion, is inducible by p53. Introduction of exogenous p53 into a glioblastoma cell line lacking wild-type p53 (U373MG) dramatically induced expression of Sema3B mRNA. An electrophoretic mobility shift assay and a reporter assay confirmed that a potential p53 binding site present in the promoter region had p53-dependent transcriptional activity. Expression of endogenous Sema3B was induced in response to genotoxic stresses caused by adriamycin treatment or UV irradiation in a p53-dependent manner. Ectopic expression of Sema3B in p53-defective cells reduced the number of colonies in colony formation assays. These results suggest that Sema3B might play some role in regulating cell growth as a mediator of p53 tumor-suppressor activity.
Ochi
Kensuke
K
Laboratory of Molecular Medicine and Genome Technology, Institute of Medical Science, University of Tokyo, Japan.
Mori
Toshiki
T
Toyama
Yoshiaki
Y
Nakamura
Yusuke
Y
Arakawa
Hirofumi
H
D001483:Base Sequence; D001665:Binding Sites; D015152:Blotting, Northern; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D003114:Colony-Forming Units Assay; D016384:Consensus Sequence; D004249:DNA Damage; D017931:DNA Primers / Q000737:chemistry; D024202:Electrophoretic Mobility Shift Assay; D020869:Gene Expression Profiling; D005909:Glioblastoma / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics*; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D039961:Semaphorins; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000528:radiation effects; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D014466:Ultraviolet Rays
D017931:DNA Primers; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; C409766:SEMA3B protein, human; D039961:Semaphorins; D016159:Tumor Suppressor Protein p53; D008156:Luciferases