ID 40618
本文ファイル
Thumnail k6373_3.pdf 746 KB
Thumnail k6373_1.pdf 360 KB
Thumnail k6373_2.pdf 321 KB
別タイトル
Kruppel様ジンクフィンガー型転写因子であるGLI-similar 1は低酸素誘導性転写因子の非古典的機構によって制御されている
著者
Elham, Khalesi
キーワード
GLIS1
Hypoxia
HIF
AP1
Gene transcription
NDC
医学
抄録(英)
GLI-similar 1 (GLIS1) is important for the reprogramming of fibroblasts into induced pluripotent stem cells (iPSCs). However, the molecular mechanisms of regulation of GLIS1 expression remain unclear. We have therefore examined GLIS1 expression in various cancer cell lines and demonstrated that GLIS1 expression was dramatically increased under hypoxic conditions. Importantly, GLIS1 expression was significantly attenuated in VHL-overexpressing renal cell carcinoma cells compared to the VHL-deficient parent control. Moreover, promoter analysis demonstrated that GLIS1 transcription was regulated by hypoxia through a hypoxia-inducible factors (HIFs)-dependent mechanism. Co-transfection experiments revealed that HIF-2a had greater potency on the GLIS1 promoter activation than HIF-1a. Subsequent studies using wild-type and mutant HIF-2a demonstrated that DNA binding activity was not necessary but TADs were critical for GLIS1 induction. Finally, co-transfection experiments indicated that HIF-2a cooperated with AP-1 family members in upregulating GLIS1 transcription. These results suggest that the hypoxic signaling pathway may play a pivotal role in regulating the reprogramming factor GLIS1, via non-canonical mechanisms involving partner transcription factor rather than by direct HIF transactivation.
言語
英語
NII資源タイプ
学位論文
広大資料タイプ
学位論文
DCMIタイプ
text
フォーマット
application/pdf
関連情報(references)
Elham Khalesi, Hideaki Nakamura, Kian Leong Lee, Andika Chandra Putra, Takahiro Fukazawa, Yumi Kawahara, Yuichi Makino, Lorenz Poellinger, Louis Yuge and Keiji Tanimoto; The Kruppel-like zinc finger transcription factor, GLI-similar 1, is regulated by hypoxia-inducible factors via non-canonical mechanisms.; Biochemical and Biophysical Research Communications, Volume 441, Issue 2, 15 November 2013, Pages 499-506 (DOI: 10.1016/j.bbrc.2013.10.083)
関連情報URL(references)
http://doi.org/10.1016/j.bbrc.2013.10.083
学位記番号
甲第6373号
授与大学
広島大学(Hiroshima University)
学位名
博士(保健学)
学位名の英名
Philosophy in Health Science
学位の種類の英名
doctoral
学位授与年月日
2014-03-23
部局名
保健学研究科