To cease or to proliferate: new insights into TCTP function from a Drosophila study.
Tor (target of rapamycin) pathway underlies a major signaling mechanism for controlling cell growth and proliferation.(1) Rheb (Ras homolog enriched in brain) is a small GTPase in the Tor pathway.(2-4) Similar to other small GTPases, Rheb cycles between a GTP-bound active state and a GDP-bound inactive state. TSC2 (tuberous sclerosis complex 2), a gene mutated in an autosomal dominant disease tuberous sclerosis, was shown to be the Rheb-GAP (GTPase activating protein).(5,6) However, a guanine nucleotide exchange factor (GEF) for Rheb had been missing. Human TCTP (translationally controlled tumor protein) has been implicated in cancer, but its function in vivo has not been clearly elucidated. Recently we reported a molecular genetic characterization of TCTP function in Drosophila.(7) Drosophila TCTP (dTCTP) displays GEF activity to Rheb and is essential for Rheb activation in organ growth. Thus, our study provides a tight linkage of dTCTP to the Rheb-TOR pathway. In this addendum, we will briefly overview our findings and discuss our perspectives for future research on TCTP.
Choi
Kwang-Wook
KW
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030 , USA. kchoi@bcm.tmc.edu
Hsu
Ya-Chieh
YC
D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D006153:Guanosine Diphosphate / Q000235:genetics / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000235:genetics / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D011494:Protein Kinases; D000076205:Ras Homolog Enriched in Brain Protein; D015398:Signal Transduction / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases; D000090324:Tumor Protein, Translationally-Controlled 1
D014408:Biomarkers, Tumor; D029721:Drosophila Proteins; D006153:Guanosine Diphosphate; D006160:Guanosine Triphosphate; D047908:Intracellular Signaling Peptides and Proteins; D020559:Monomeric GTP-Binding Proteins; D009479:Neuropeptides; D019869:Phosphatidylinositol 3-Kinases; D011494:Protein Kinases; D000076205:Ras Homolog Enriched in Brain Protein; D058570:TOR Serine-Threonine Kinases; D000090324:Tumor Protein, Translationally-Controlled 1; C490212:Rheb protein, Drosophila; C517693:TCTP protein, Drosophila; C000715647:TPT1 protein, human; C416303:target of rapamycin protein, Drosophila