Reference Report

Reference
Citation	Hsu, Y.C., Chern, J.J., Cai, Y., Liu, M., Choi, K.W. (2007). Drosophila TCTP is essential for growth and proliferation through regulation of dRheb GTPase. Nature 445(7129): 785--788. (Export to RIS)
FlyBase ID	FBrf0192022
Publication Type	Research paper
PubMed ID	17301792
PubMed Abstract	Cellular growth and proliferation are coordinated during organogenesis. Misregulation of these processes leads to pathological conditions such as cancer. Tuberous sclerosis (TSC) is a benign tumour syndrome caused by mutations in either TSC1 or TSC2 tumour suppressor genes. Studies in Drosophila and other organisms have identified TSC signalling as a conserved pathway for growth control. Activation of the TSC pathway is mediated by Rheb (Ras homologue enriched in brain), a Ras superfamily GTPase. Rheb is a direct target of TSC2 and is negatively regulated by its GTPase-activating protein activity. However, molecules required for positive regulation of Rheb have not been identified. Here we show that a conserved protein, translationally controlled tumour protein (TCTP), is an essential new component of the TSC-Rheb pathway. Reducing Drosophila TCTP (dTCTP) levels reduces cell size, cell number and organ size, which mimics Drosophila Rheb (dRheb) mutant phenotypes. dTCTP is genetically epistatic to Tsc1 and dRheb, but acts upstream of dS6k, a downstream target of dRheb. dTCTP directly associates with dRheb and displays guanine nucleotide exchange activity with it in vivo and in vitro. Human TCTP (hTCTP) shows similar biochemical properties compared to dTCTP and can rescue dTCTP mutant phenotypes, suggesting that the function of TCTP in the TSC pathway is evolutionarily conserved. Our studies identify TCTP as a direct regulator of Rheb and a potential therapeutic target for TSC disease.
DOI	10.1038/nature05528
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Language of Publication	English
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Publication Type	Journal
Abbreviation	Nature
Title	Nature
Publication Year	1869-
ISBN/ISSN	0028-0836
Data from Reference
Aberrations (1)
	Df(3R)M-Kx1
Alleles (17)
	BacA\p35^Scer\UAS.cHa CycE^Scer\UAS.cRa InR^Scer\UAS.cHa Rheb^{Act5C.cHa.T:Hsap\MYC} Rheb^Scer\UAS.cSa S6k^l-1 Scer\GAL4^Act.PU Scer\GAL4^ey.PH Scer\GAL4^nub.PK Scer\GAL4^ptc-559.1 Scer\GAL4^tub.PU Tctp^{dsRNA.Scer\UAS} Tctp^{E12V.Scer\UAS} Tctp^EY09182 Tctp^h59 Tctp^Scer\UAS.cHa Tsc1^Q600X
Constructs (9)
	P{GAL4-ey.H} P{nub-GAL4.K} P{tub-GAL4.U} P{UAS-CycE.R} P{UAS-InR.H} P{UAS-p35.H} P{UAS-Tctp.E12V} P{UAS-Tctp.H} P{UAS-Tctp.RNAi}
Genes (9)
	BacA\p35 CycE InR Rheb S6k Scer\GAL4 T:Hsap\MYC Tctp Tsc1
Insertions (2)
	P{EPgy2}Tctp^EY09182 P{GawB}ptc^559.1
Natural transposons (1)
	P-element