SNIP1 is a candidate modifier of the transcriptional activity of c-Myc on E box-dependent target genes.
Using a yeast two-hybrid screen, we found that SNIP1 (Smad nuclear-interacting protein 1) associates with c-Myc, a key regulator of cell proliferation and transformation. We demonstrate that SNIP1 functions as an important regulator of c-Myc activity, binding the N terminus of c-Myc through its own C terminus, and that SNIP1 enhances the transcriptional activity of c-Myc both by stabilizing it against proteosomal degradation and by bridging the c-Myc/p300 complex. These effects of SNIP1 on c-Myc likely contribute to synergistic effects of SNIP1, c-Myc, and H-Ras in inducing formation of foci in an in vitro transformation assay and also in supporting anchorage-independent growth. The significant association of SNIP1 and c-Myc staining in a non-small cell lung cancer tissue array is further evidence that their activities might be linked and suggests that SNIP1 might be an important modulator of c-Myc activity in carcinogenesis.
Fujii
Makiko
M
Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892; Department of Biochemistry, Jichi Medical University, Tochigi 329-0498, Japan. Electronic address: fujiim@jichi.ac.jp.
Lyakh
Lyudmila A
LA
Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892.
Bracken
Cameron P
CP
Division of Gene Regulation and Expression, College of Life Sciences, University of Dundee, MSI/WTB Complex, Dow Street, Dundee, DD1 5EH, United Kingdom.
Fukuoka
Junya
J
Laboratory of Population Genetics, National Cancer Institute, Building 41, Room D702, Bethesda, Maryland 20892.
Hayakawa
Morisada
M
Department of Biochemistry, Jichi Medical University, Tochigi 329-0498, Japan.
Tsukiyama
Tadasuke
T
Cancer and Developmental Biology Laboratory, National Cancer Institute at Frederick, Frederick, Maryland 21702.
Soll
Steven J
SJ
Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892.
Harris
Melissa
M
Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892.
Rocha
Sonia
S
Division of Gene Regulation and Expression, College of Life Sciences, University of Dundee, MSI/WTB Complex, Dow Street, Dundee, DD1 5EH, United Kingdom.
Roche
Kevin C
KC
Division of Gene Regulation and Expression, College of Life Sciences, University of Dundee, MSI/WTB Complex, Dow Street, Dundee, DD1 5EH, United Kingdom.
Tominaga
Shin-Ichi
SI
Department of Biochemistry, Jichi Medical University, Tochigi 329-0498, Japan.
Jen
Jin
J
Laboratory of Population Genetics, National Cancer Institute, Building 41, Room D702, Bethesda, Maryland 20892.
Perkins
Neil D
ND
Division of Gene Regulation and Expression, College of Life Sciences, University of Dundee, MSI/WTB Complex, Dow Street, Dundee, DD1 5EH, United Kingdom.
Lechleider
Robert J
RJ
Molecular Oncology Research Unit, National Cancer Institute, 10/12N226, Bethesda, Maryland 20892. Electronic address: lechleiderr@mail.nih.gov.
Roberts
Anita B
AB
Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892.
D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D002460:Cell Line; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D016601:RNA-Binding Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D044786:S-Phase Kinase-Associated Proteins / Q000378:metabolism; D012680:Sensitivity and Specificity; D046888:Tissue Array Analysis; D014158:Transcription, Genetic; D020798:Two-Hybrid System Techniques
D047908:Intracellular Signaling Peptides and Proteins; D016271:Proto-Oncogene Proteins c-myc; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D044786:S-Phase Kinase-Associated Proteins; C411545:SNIP1 protein, human