RRC ID 28644
Author Kurabe N, Katagiri K, Komiya Y, Ito R, Sugiyama A, Kawasaki Y, Tashiro F.
Title Deregulated expression of a novel component of TFTC/STAGA histone acetyltransferase complexes, rat SGF29, in hepatocellular carcinoma: possible implication for the oncogenic potential of c-Myc.
Journal Oncogene
Abstract c-Myc N-terminal conserved domains, MbI and MbII, are essential for c-Myc-mediated transformation and transactivation. These domains recruit the STAGA (SPT3-TAF9-GCN5-acetyltransferase) coactivator complex, but not TFTC (TATA-binding protein-free TAF-containing) to the target gene promoter. Although components of this complex are well conserved between yeast and mammals, four mammalian orthologs of yeast SPT8, SPT20, SGF11 and SGF29 remain to be identified. Here, we isolated a rat ortholog of yeast SGF29, a component of yeast SAGA (SPT-ADA-GCN5-acetyltransferase) complex. Both rat (r) SGF29 and c-myc mRNAs were overexpressed in five out of the eight tested rodent tumor cells. rSGF29 directly interacted with rADA3 and co-immunoprecipitated with two other TFTC/STAGA components, rGCN5 and rSPT3. rSGF29 was recruited to the c-Myc target gene promoters together with c-Myc, and it activated c-Myc target gene expressions. Downregulation of rSGF29 suppressed the expression of c-Myc target genes and inhibited anchorage-independent growth and tumorigenicity and lung metastasis of rat hepatoma K2 cells when injected into nude mice. These results show that rSGF29 is a novel component of TFTC/STAGA complexes and could be involved in the c-Myc-mediated malignant transformation.
Volume 26(38)
Pages 5626-34
Published 2007-8-16
DOI 10.1038/sj.onc.1210349
PII 1210349
PMID 17334388
MeSH Animals Blotting, Northern Blotting, Western COS Cells Carcinoma, Hepatocellular / genetics Carcinoma, Hepatocellular / metabolism Carcinoma, Hepatocellular / pathology* Cell Line, Tumor Chlorocebus aethiops Gene Expression Regulation Green Fluorescent Proteins / genetics Green Fluorescent Proteins / metabolism Histone Acetyltransferases / genetics Histone Acetyltransferases / metabolism* Liver Neoplasms, Experimental / genetics Liver Neoplasms, Experimental / metabolism Liver Neoplasms, Experimental / pathology* Mice Mice, Nude Oligonucleotides, Antisense / genetics Protein Subunits / genetics Protein Subunits / metabolism Proto-Oncogene Proteins c-myc / genetics Proto-Oncogene Proteins c-myc / metabolism* Rats Recombinant Fusion Proteins / genetics Recombinant Fusion Proteins / metabolism Transcriptional Activation Transfection Tumor Burden Two-Hybrid System Techniques
IF 7.971
Times Cited 20
DNA material pcDNA3/HA-rSGF29 (RDB07944)