Genomes and Genes
Affiliation: Harvard University
- Kaelin W. Proline hydroxylation and gene expression. Annu Rev Biochem. 2005;74:115-28 pubmed..The existence of three human EGLN family members, as well as other putative hydroxylases, raises the possibility that this signal is used in other contexts by other proteins. ..
- Kaelin W, Ratcliffe P. Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway. Mol Cell. 2008;30:393-402 pubmed publisher..HIF affects signaling pathways that influence development, metabolism, inflammation, and integrative physiology. Accordingly, HIF-modulatory drugs are now being developed for diverse diseases. ..
- Olenchock B, Moslehi J, Baik A, Davidson S, Williams J, Gibson W, et al. EGLN1 Inhibition and Rerouting of Î±-Ketoglutarate Suffice for Remote Ischemic Protection. Cell. 2016;164:884-95 pubmed publisher..Egln1 loss causes accumulation of circulating Î±KG, which drives hepatic production and secretion of kynurenic acid (KYNA) that is necessary and sufficient to mediate cardiac ischemic protection in this setting. ..
- Kaelin W. The von Hippel-Lindau tumor suppressor gene and kidney cancer. Clin Cancer Res. 2004;10:6290S-5S pubmed..Genotype-phenotype correlations in VHL disease suggest, however, that pVHL has targets in addition to HIF. Elucidating these targets should provide a more complete picture of how pVHL suppresses tumor growth. ..
- Kaelin W. The von Hippel-Lindau tumor suppressor protein and clear cell renal carcinoma. Clin Cancer Res. 2007;13:680s-684s pubmed
- Chakraborty A, Nakamura E, Qi J, Creech A, Jaffe J, Paulk J, et al. HIF activation causes synthetic lethality between the VHL tumor suppressor and the EZH1 histone methyltransferase. Sci Transl Med. 2017;9: pubmed publisher..Therefore, targeting EZH1 could be therapeutically useful in ccRCC. ..
- Gao W, Li W, Xiao T, Liu X, Kaelin W. Inactivation of the PBRM1 tumor suppressor gene amplifies the HIF-response in VHL-/- clear cell renal carcinoma. Proc Natl Acad Sci U S A. 2017;114:1027-1032 pubmed publisher..Biochemical and functional studies linked growth suppression by BAF180 to its ability to form a canonical PBAF complex containing BRG1 that dampens the HIF transcriptional signature. ..
- Briggs K, Koivunen P, Cao S, Backus K, Olenchock B, Patel H, et al. Paracrine Induction of HIF by Glutamate in Breast Cancer: EglN1 Senses Cysteine. Cell. 2016;166:126-39 pubmed publisher..EglN1, the main HIF? prolyl-hydroxylase, undergoes oxidative self-inactivation in the absence of cysteine both in biochemical assays and in cells, resulting in HIF1? accumulation. Therefore, EglN1 senses both oxygen and cysteine. ..
- Kaelin W. SDH5 mutations and familial paraganglioma: somewhere Warburg is smiling. Cancer Cell. 2009;16:180-2 pubmed publisher..Moreover, they detected SDH5 mutations in a large kindred with familial paraganglioma. ..
- Kaelin W. The emerging p53 gene family. J Natl Cancer Inst. 1999;91:594-8 pubmed..Additional studies are required to determine the role, if any, that p73 and p51 play in cell growth control and carcinogenesis. ..
- Lu G, Zhang Q, Huang Y, Song J, Tomaino R, Ehrenberger T, et al. Phosphorylation of ETS1 by Src family kinases prevents its recognition by the COP1 tumor suppressor. Cancer Cell. 2014;26:222-34 pubmed publisher..These findings expand the list of potential COP1 substrates to include proteins whose COP1-binding sites are subject to regulatory phosphorylation and provide insights into transformation by Src family kinases. ..
- Kaelin W, McKnight S. Influence of metabolism on epigenetics and disease. Cell. 2013;153:56-69 pubmed publisher..Here, we review literature pertinent to hypothetical connections between metabolic and epigenetic states in eukaryotic cells. ..