The caudal homeodomain protein activates Drosophila E2F gene expression.
The Drosophila caudal homeobox gene is required for definition of the anteroposterior axis and for gut development, and CDX1 and CDX2, human homologs, play crucial roles in the regulation of cell proliferation and differentiation in the intestine. Most studies have indicated tumor suppressor functions of Cdx2, with inhibition of proliferation, while the effects of Cdx1 are more controversial. The influence of Drosophila Caudal on cell proliferation is unknown. In this study, we found three potential Caudal binding sequences in the 5'-flanking region of the Drosophila E2F (DE2F) gene and showed by transient transfection assays that they are involved in Caudal transactivation of the dE2F gene promoter. Analyses with transgenic flies carrying an E2F-lacZ fusion gene, with and without mutation in the Caudal binding site, indicated that the Caudal binding sites are required for expression of dE2F in living flies. Caudal-induced E2F expression was also confirmed with a GAL4-UAS system in living flies. In addition, ectopic expression of Caudal with heat-shock promotion induced melanotic tumors in larvae. These results suggest that Caudal is involved in regulation of proliferation through transactivation of the E2F gene in Drosophila.
Hwang
Mi-Sun
MS
Department of Molecular Biology, Pusan National University, Pusan 609-735, Korea.
Kim
Young-Shin
YS
Choi
Na-Hyun
NH
Park
Jae-Hong
JH
Oh
Eun-Jin
EJ
Kwon
Eun-Jeong
EJ
Yamaguchi
Masamitsu
M
Yoo
Mi-Ae
MA
D024506:5' Flanking Region; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D004330:Drosophila / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D029721:Drosophila Proteins / Q000096:biosynthesis / Q000235:genetics*; D050684:E2F Transcription Factors; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000502:physiology*; D011401:Promoter Regions, Genetic; D015534:Trans-Activators / Q000502:physiology*; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D015533:Transcriptional Activation
D029721:Drosophila Proteins; D050684:E2F Transcription Factors; C496298:E2f1 protein, Drosophila; D018398:Homeodomain Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C084564:cad protein, Drosophila