2019諾貝爾獎精彩研究回顧-生醫獎

TAG: 學術傳播

2019/10/17

眾所矚目的諾貝爾獎揭曉,今年的生醫獎由由美國癌症學家凱林(William G. Kaelin Jr)、英國醫學家拉特克利夫(Peter J. Ratcliffe)和美國醫學家塞門扎(Gregg L. Semenza)共同獲得。

這三位學者以研究「細胞如何適應氧氣供應量的變化」而獲獎,其發現為貧血、癌症、其他疾病的新治療策略打開新大門。

氧氣對地球上所有生物都是至關重要的元素,幾乎所有動物體內細胞的粒線體,都利用氧氣才能將食物轉化為能量,但長期以來,科學家們並不清楚細胞如何去適應體內氧氣值的變化。而美國癌症學家威廉·喬治·凱林(William George Kaelin)、英國分子生物學家彼得·拉特克利夫(Sir Peter J. Ratcliffe)、美國醫學家格雷格·塞門扎(Gregg L. Semenza)3 人,發現了細胞如何感應與適應氧氣供應不斷變化的關鍵分子機制,可以調節基因活性去應對不同的氧氣量。

 

與此發現的主要研究文獻如下:

1. Semenza, G.L, Nejfelt, M.K., Chi, S.M. & Antonarakis, S.E. (1991). Hypoxia-inducible nuclear factors bind to an enhancer element located 3’ to the human erythropoietin gene. Proc Natl Acad Sci USA, 88, 5680-5684

2. Wang, G.L., Jiang, B.-H., Rue, E.A. & Semenza, G.L. (1995). Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension.  Proc Natl Acad Sci USA, 92, 5510-5514

3. Maxwell, P.H., Wiesener, M.S., Chang, G.-W., Clifford, S.C., Vaux, E.C., Cockman, M.E., Wykoff, C.C., Pugh, C.W., Maher, E.R. & Ratcliffe, P.J. (1999). The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature, 399, 271-275

4. Ivan, M., Kondo, K., Yang, H., Kim, W., Valiando, J., Ohh, M., Salic, A., Asara, J.M., Lane, W.S. & Kaelin Jr., W.G. (2001) HIFa targeted for VHL-mediated destruction by proline hydroxylation: Implications for O2 sensing. Science, 292, 464-468

5. Jaakkola, P., Mole, D.R., Tian, Y.-M., Wilson, M.I., Gielbert, J., Gaskell, S.J., von Kriegsheim, A., Heberstreit, H.F., Mukherji, M., Schofield, C.J., Maxwell, P.H., Pugh, C.W. & Ratcliffe, P.J. (2001). Targeting of HIF-α to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation. Science, 292, 468-472

 

此外,三位得獎者與此相關的研究,以下出版社彙整相關文獻,部分出版社也提供免費閱覽:

1. Annual Reviews: 2019 Nobel Prize in Physiology or Medicine

(1) The von Hippel-Lindow Tumor Suppressor Protein, W. G. Kaelin, Jr., 2018 Annual Review of Cancer Biology 
(2) Pharmacologic Targeting of Hypoxia-Inducible Factors, G. L. Semenza, 2019 Annual Review of Pharmacology and Toxicology 
(3) Oxygen Sensing, Hypoxia-Inducible Factors, and Disease Pathophysiology, G. L. Semenza, 2014 Annual Review of Pathology: Mechanisms of Disease 
(4) Hypoxia-Inducible Factor 1 and Cardiovascular Disease, G. L. Semenza, 2014 Annual Review of Physiology

2. Nature: Nobel Prize in Physiology or Medicine 2019

3. Science: Medicine nobel honors work on cellular system to sense oxygen levels.

 

資料來源:

NOBEL PRIZE. (2019). The nobel prize in physiology or medicine 2019

Case 報科學(2019)。【2019 年諾貝爾生醫獎】一窺細胞如何「氧」尊處優。 

TechNews(2019)。2019 諾貝爾生醫獎 3 名得主出爐,發現細胞適應含氧量變化的關鍵機制

 

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