RRC ID 49515
著者 Wang XF, Shen Y, Cheng Q, Fu CL, Zhou ZZ, Hirose S, Liu QX.
タイトル Apontic directly activates hedgehog and cyclin E for proper organ growth and patterning.
ジャーナル Sci Rep
Abstract Hedgehog (Hh) signaling pathway and Cyclin E are key players in cell proliferation and organ development. Hyperactivation of hh and cyclin E has been linked to several types of cancer. However, coordination of the expression of hh and cyclin E was not well understood. Here we show that an evolutionarily conserved transcription factor Apontic (Apt) directly activates hh and cyclin E through its binding site in the promoter regions of hh and cyclin E. This Apt-dependent proper expression of hh and cyclin E is required for cell proliferation and development of the Drosophila wing. Furthermore, Fibrinogen silencer-binding protein (FSBP), a mammalian homolog of Apt, also positively regulates Sonic hh (Shh), Desert hh (Dhh), Cyclin E1 (CCNE1) and Cyclin E2 (CCNE2) in cultured human cells, suggesting evolutionary conservation of the mechanism. Apt-mediated expression of hh and cyclin E can direct proliferation of Hh-expressing cells and simultaneous growth, patterning and differentiation of Hh-recipient cells. The discovery of the simultaneous expression of Hh and principal cell-cycle regulator Cyclin E by Apt implicates insight into the mechanism by which deregulated hh and cyclin E promotes tumor formation.
巻・号 7(1)
ページ 12470
公開日 2017-9-29
DOI 10.1038/s41598-017-12766-w
PII 10.1038/s41598-017-12766-w
PMID 28963499
PMC PMC5622130
MeSH Animals Base Sequence Binding Sites Biological Evolution Body Patterning / genetics* Carrier Proteins / genetics Carrier Proteins / metabolism Cell Proliferation Cell Transformation, Neoplastic / genetics Cell Transformation, Neoplastic / metabolism Cell Transformation, Neoplastic / pathology Conserved Sequence Cyclin E / genetics* Cyclin E / metabolism Cyclins / genetics Cyclins / metabolism DNA-Binding Proteins / genetics* DNA-Binding Proteins / metabolism Drosophila Proteins / genetics* Drosophila Proteins / metabolism Drosophila melanogaster / cytology Drosophila melanogaster / genetics* Drosophila melanogaster / growth & development Drosophila melanogaster / metabolism Female Fetal Proteins / genetics Fetal Proteins / metabolism Gene Expression Regulation, Developmental HEK293 Cells Hedgehog Proteins / genetics* Hedgehog Proteins / metabolism Humans Intracellular Signaling Peptides and Proteins Male Oncogene Proteins / genetics Oncogene Proteins / metabolism Promoter Regions, Genetic Protein Binding Signal Transduction Transcription Factors / genetics* Transcription Factors / metabolism Wings, Animal / cytology Wings, Animal / growth & development Wings, Animal / metabolism*
IF 3.998
引用数 4
リソース情報
ショウジョウバエ CAS-0001 TBX-0002 TBX-0004 TBX-0008 TBX-0010