The activation of TC10, a Rho small GTPase, contributes to v-Rel-mediated transformation.
v-Rel is the oncogenic member of the Rel/NF-kappaB family of transcription factors and transforms hematopoietic cells and fibroblasts. Differential display was employed to identify target genes that exhibit altered expression in v-Rel transformed cells. One of the cDNAs identified encodes the chicken ortholog of TC10, a member of the Rho small GTPase family. The expression of TC10 was increased in v-Rel-transformed chicken embryonic fibroblasts (CEFs) 3 to 6-fold relative to control cells at both the RNA and protein levels. An elevated level of active, GTP-bound TC10 was also detected in v-Rel-transformed cells relative to control cells. Expression of a dominant-negative TC10 mutant (TC10T32N) decreased the colony formation potential of v-Rel-transformed cells. Furthermore, overexpression of wild-type TC10 or a gain-of-function mutant (TC10Q76L) greatly enhanced the ability of v-Rel transformed CEFs to form colonies in soft agar. In addition to enhance the transformation potential of v-Rel, the overexpression of wild-type TC10 or the gain-of-function mutant alone enhanced the saturation density of CEFs and was sufficient for their anchorage-independent growth in vitro. These results indicate that elevated TC10 activity contributes to v-Rel-mediated transformation of CEFs and demonstrate for the first time that a Rho factor alone is capable of inducing the in vitro transformation of primary cells.
Tong
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Section of Molecular Genetics and Microbiology and the Institute of Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712-1095, USA.
Liss
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You
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Bose
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HR
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002642:Chick Embryo; D003001:Cloning, Molecular; D015972:Gene Expression Regulation, Neoplastic; D020573:Genes, rel; D006801:Humans; D008969:Molecular Sequence Data; D020572:Oncogene Proteins v-rel / Q000378:metabolism; D014176:Protein Biosynthesis; D020741:rho GTP-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D020572:Oncogene Proteins v-rel; D020741:rho GTP-Binding Proteins