کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10752391 | 1050327 | 2015 | 40 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
HIF-1α suppressing small molecule, LW6, inhibits cancer cell growth by binding to calcineurin b homologous protein 1
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کلمات کلیدی
FBSHUVECHIF-α3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide - 3- (4،5-dimethylthiazol-2-yl) -2،5-difenyl tetrazolium bromideMTT - MTTSmall interfering RNA - RNA تداخل کوچکsiRNA - siRNAAngiogenesis - آنژیوژنزSPR - تشدید پلاسمون سطحیSurface plasmon resonance - تشدید پلاسمون سطحیDissociation constant - حد تفکیکfetal bovine serum - سرم جنین گاوHuman umbilical vein endothelial cell - سلول اندوتلیالی ورید ناقل انسانیTarget identification - شناسایی هدفhypoxia-inducible factor-1α - عامل القاء شده با هیپوکسی 1αhypoxia inducible factor-1 alpha - هیپوکسی القاء عامل 1 الف
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Hypoxia inducible factor-1 alpha (HIF-1α) plays an important role in angiogenesis and metastasis and is a promising therapeutic target for the development of anti-cancer drugs. We recently developed a new synthetic small molecule inhibitor of HIF-1α, LW6, which results in inhibition of angiogenesis. To investigate its underlying mechanism, target protein identification was conducted by reverse chemical proteomics using phage display. We identified calcineurin b homologous protein 1 (CHP1) as a target protein of LW6, which specifically binds to CHP1 in a Ca2+ dependent manner. Covalent labeling of LW6 using photoaffinity and click chemistry demonstrated its co-localization with CHP1 in live cells. HIF-1α was decreased by CHP1 knockdown in HepG2 cells, and angiogenesis was not induced in HUVEC cells by treatment with conditioned media from CHP1 knockdown cells compared to the control. These data demonstrated that LW6 inhibited HIF-1α stability via direct binding with CHP1 resulting in suppression of angiogenesis, providing a new insight into the role of CHP1 in HIF-1α regulation. LW6 could serve as a new chemical probe to explore CHP1 function.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 458, Issue 1, 27 February 2015, Pages 14-20
Journal: Biochemical and Biophysical Research Communications - Volume 458, Issue 1, 27 February 2015, Pages 14-20
نویسندگان
Beom Seok Kim, Kyeong Lee, Hye Jin Jung, Deepak Bhattarai, Ho Jeong Kwon,