Cloning, characterization of chTC10, a Rho small GTPase, its regulation by Rel/NF-kappaB family members c-Rel and v-Rel, and its role in v-Rel-mediated transformation of fibroblasts

dc.contributor.advisorBose, Henry R.en
dc.creatorTong, Shunen
dc.date.accessioned2011-07-25T21:56:45Zen
dc.date.available2011-07-25T21:56:45Zen
dc.date.issued2003-05en
dc.descriptiontexten
dc.description.abstractv-Rel is the oncogenic member of Rel/NF-κB family of transcription factors and transforms hematopoietic cells and fibroblasts. Differential display was employed to identify target genes that are regulated by v-Rel. By using this technique, one gene whose expression is upregulated by v-Rel in chicken embryonic fibroblasts (CEF) was found to encode chTC10, the chicken homolog of TC10, a member of the Rho small GTPase family. The coding region of chTC10 was cloned and shown to encode a 214 amino acids protein sharing 93% identity with human TC10. chTC10 messenger RNA is mainly expressed in heart, skeletal muscle, spleen, and bursa, and is expressed at relatively lower levels in thymus, fat, midbrain, stomach, small intestine, skin and testis from chicken. The chTC10 mRNA and protein levels were increased in v-Rel- or c-Relexpressing CEF. Elevated amounts of GTP-bound chTC10 were also detected in v-Rel-transformed CEF and c-Rel-expressing CEF. chTC10 induced some morphological changes in CEF that were not as obvious as those in mammalian fibroblasts. chTC10Q76L, when highly expressed in CEF, induced numerous short filopodia and cells became rounder. Both wild type and a gain-of-function mutant (chTC10Q76L) enhanced the anchorage-independent growth ability of CEF. Co-expression of chTC10Q76L or chTC10 with v-Rel greatly enhanced CEF colony formation ability in soft agar. By contrast, expression of the dominant negative mutant (chTC10T32N) decreased the colony formation potential of v-Rel. Furthermore, chTC10Q76L increased the saturation density of CEF and this ability was enhanced by its cooperation with v-Rel. These results indicate that chTC10 contributes to transformation of primary fibroblasts by increasing the colony formation ability in soft agar and by increasing cell saturation density. The induction of chTC10 expression and activity contributes to v-Rel-mediated transformation of CEF. In addition, chTC10Q76L activates c-Jun N-terminal kinase (JNK) in response to serum starvation. JNK activity was greatly induced in v-Reltransformed CEF when cells were grown without extracellular matrix. Coexpression with chTC10T32N greatly decreased this activity, suggesting that chTC10 is important for activation of JNK in v-Rel-transformed CEF, and that chTC10 may induce transformation through the JNK pathway.
dc.description.departmentBiological Sciences, School ofen
dc.format.mediumelectronicen
dc.identifier.urihttp://hdl.handle.net/2152/12518en
dc.language.isoengen
dc.rightsCopyright is held by the author. Presentation of this material on the Libraries' web site by University Libraries, The University of Texas at Austin was made possible under a limited license grant from the author who has retained all copyrights in the works.en
dc.rights.restrictionRestricteden
dc.subjectRho GTPasesen
dc.subjectCells--Growth--Regulationen
dc.subjectFibroblastsen
dc.titleCloning, characterization of chTC10, a Rho small GTPase, its regulation by Rel/NF-kappaB family members c-Rel and v-Rel, and its role in v-Rel-mediated transformation of fibroblastsen
thesis.degree.departmentBiological Sciences, School ofen
thesis.degree.disciplineMolecular Biologyen
thesis.degree.grantorThe University of Texas at Austinen
thesis.degree.levelDoctoralen
thesis.degree.nameDoctor of Philosophyen

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