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今年的“拉斯克基础医学奖”授予三位在人以及大多数动物细胞感知、适应氧气的变化机制方面做出杰出贡献的医学研究者。他们分别是来自哈佛医学院Dana-Farber癌症研究所的William G. Kaelin、英国牛津大学弗朗西斯·克里克研究所(Francis Crick Institute)的Peter J. Ratcliffe以及约翰霍普金斯医学院(Johns Hopkins University School of Medicine)的Gregg Semenza。http://blog.sciencenet.cn/home.php?mod=space&uid=280034&do=blog&id=1002833
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Oxygen Sensing by Metazoans: The Central Role of the HIF Hydroxylase Pathway
Summary HIF plays a central role in the transcriptional response to changes in oxygen availability. The PHD family of oxygen-dependent prolyl hydroxylases plays a pivotal role in regulating HIF stabili…
Mammalian target of rapamycin (mTOR) is a central regulator of protein synthesis whose activity is modulated by a variety of signals. Energy depletion and hypoxia result in mTOR inhibition. While en…
The tyrosine kinase c-Abl regulates p73 in apoptotic response to cisplatin-induced DNA damage.
Cancer chemotherapeutic agents such as cisplatin exert their cytotoxic effect by inducing DNA damage and activating programmed cell death (apoptosis). The tumour-suppressor protein p53 is an imp…
THE CONCEPT OF SYNTHETIC LETHALITY IN THE CONTEXT OF ANTICANCER THERAPY
Two genes are synthetic lethal if mutation of either alone is compatible with viability but mutation of both leads to death. So, targeting a gene that is synthetic lethal to a cancer- relevant mutation shoul…
Role of VHL Gene Mutation in Human Cancer
E2F-1 Functions in Mice to Promote Apoptosis and Suppress Proliferation
Members of the E2F transcription factor family (E2F-1–E2F-5) are believed to be critical positive regulators of cell cycle progression in eukaryotes although the in vivo functions of the individual E2Fs ha…
Structure of the VHL-ElonginC-ElonginB Complex: Implications for VHL Tumor Suppressor Function
Mutation of the VHL tumor suppressor is associated with the inherited von Hippel–Lindau (VHL) cancer syndrome and the majority of kidney cancers. VHL binds the ElonginC-ElonginB complex and re…
Molecular basis of the VHL hereditary cancer syndrome
Expression cloning of a cDNA encoding a retinoblastoma-binding protein with E2F-like properties
Abstract An expression vector was modified to permit the rapid synthesis of purified, 32P-labeled, glutathione S-transferase (GST)-retinoblastoma (RB) fusion proteins. The products were used to scree…
Inhibition of HIF is necessary for tumor suppression by the von Hippel-Lindau protein
Inactivation of the von Hippel-Lindau tumor suppressor gene is linked to the development of hereditary (VHL Disease-associated) and sporadic clear cell carcinoma of the kidney. The VHL gene product…
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