BACKGROUND: Eleven-nineteen lysine-rich leukemia (ELL) plays an important role in tumorigenesis and animal development. HIF-1 is a transcriptional factor that functions as a master regulator of O(2) homeostasis. Our previous studies showed that a binding partner of ELL, U19/Eaf2, can modulate HIF-1alpha activity and hypoxia response, suggesting that ELL may also influence HIF-1alpha pathway and hypoxia response. METHODS: Co-localization and co-immunoprecipitation were performed to test the interaction between ELL and HIF-1alpha. PC3 cells with stable ELL knockdown and PC3 cells with stable ELL overexpression, along with their controls, were established using lentiviral expression system. Western blot and real-time PCR were performed to test the effect of ELL on HIF-1alpha protein and its down-stream gene transcription. To elucidate potential effect of hypoxia on ELL, cell growth and colony formation assays were performed using PC3 subline with stable ELL overexpression. RESULTS: ELL is associated with HIF-1alpha in transfected cells. In PC3 prostate cancer cells, ELL inhibited HIF-1alpha protein level and down-stream gene expression. As expected, ELL inhibited cell growth and colony formation under normoxia. Interestingly, the inhibition was alleviated under hypoxia. CONCLUSIONS: Our findings suggest that ELL and HIF-1alpha are binding partners and can modulate the functions of each other in hypoxia.
BACKGROUND:Eleven-nineteen lysine-rich leukemia (ELL) plays an important role in tumorigenesis and animal development. HIF-1 is a transcriptional factor that functions as a master regulator of O(2) homeostasis. Our previous studies showed that a binding partner of ELL, U19/Eaf2, can modulate HIF-1alpha activity and hypoxia response, suggesting that ELL may also influence HIF-1alpha pathway and hypoxia response. METHODS: Co-localization and co-immunoprecipitation were performed to test the interaction between ELL and HIF-1alpha. PC3 cells with stable ELL knockdown and PC3 cells with stable ELL overexpression, along with their controls, were established using lentiviral expression system. Western blot and real-time PCR were performed to test the effect of ELL on HIF-1alpha protein and its down-stream gene transcription. To elucidate potential effect of hypoxia on ELL, cell growth and colony formation assays were performed using PC3 subline with stable ELL overexpression. RESULTS:ELL is associated with HIF-1alpha in transfected cells. In PC3 prostate cancer cells, ELL inhibited HIF-1alpha protein level and down-stream gene expression. As expected, ELL inhibited cell growth and colony formation under normoxia. Interestingly, the inhibition was alleviated under hypoxia. CONCLUSIONS: Our findings suggest that ELL and HIF-1alpha are binding partners and can modulate the functions of each other in hypoxia.
Authors: Joo Won Jeong; Moon Kyoung Bae; Mee Young Ahn; Se Hee Kim; Tae Kwon Sohn; Myung Ho Bae; Mi Ae Yoo; Eun Joo Song; Kong Joo Lee; Kyu Won Kim Journal: Cell Date: 2002-11-27 Impact factor: 41.582
Authors: K Mitani; T Yamagata; C Iida; H Oda; K Maki; M Ichikawa; T Asai; H Honda; M Kurokawa; H Hirai Journal: Biochem Biophys Res Commun Date: 2000-12-20 Impact factor: 3.575
Authors: H Zhong; A M De Marzo; E Laughner; M Lim; D A Hilton; D Zagzag; P Buechler; W B Isaacs; G L Semenza; J W Simons Journal: Cancer Res Date: 1999-11-15 Impact factor: 12.701
Authors: Laura E Pascal; Khalid Z Masoodi; June Liu; Xiaonan Qiu; Qiong Song; Yujuan Wang; Yachen Zang; Tiejun Yang; Yao Wang; Lora H Rigatti; Uma Chandran; Leandro M Colli; Ricardo Z N Vencio; Yi Lu; Jian Zhang; Zhou Wang Journal: J Endocrinol Date: 2017-11 Impact factor: 4.286
Authors: Sami Heikkinen; Sami Väisänen; Petri Pehkonen; Sabine Seuter; Vladimir Benes; Carsten Carlberg Journal: Nucleic Acids Res Date: 2011-08-16 Impact factor: 16.971