{"id":2470,"date":"2013-04-07T17:37:02","date_gmt":"2013-04-07T17:37:02","guid":{"rendered":"http:\/\/thetravellerslastjourney.com\/shai\/2018\/12\/23\/1010-revision-v1\/"},"modified":"2019-07-13T09:36:50","modified_gmt":"2019-07-13T09:36:50","slug":"science-review-oncometabolites-2","status":"publish","type":"post","link":"https:\/\/thetravellerslastjourney.com\/shai\/2013\/04\/07\/science-review-oncometabolites-2\/","title":{"rendered":"Science Review: Oncometabolites"},"content":{"rendered":"<p style=\"text-align: justify;\"><strong>Concept<\/strong>: Oncometabolites. Also: Dynamic interplay of metabolome and epigenome.<\/p>\n<p style=\"text-align: justify;\"><strong>Source<\/strong>: News and Views\u00a0in <em><a href=\"https:\/\/www.nature.com\/articles\/496038a\">Nature\u00a0(April 3, 2013)<\/a><\/em> of a study published in Science.<\/p>\n<ul>\n<li style=\"text-align: justify;\"><strong>Background<\/strong>: It was already known that mutations in proteins involved in metabolism may be associated with cancer, but this is the first study to show that a metabolite may be sufficient for oncogenesis. Previous studies identified mutations in isocitrate dehydrogenase 1 and 2 (IDH1\/2) in (75% of) brain tumours and (20% of) leukemia. IDH1\/2 act in the citric acid cycle to convert isocitrate to alpha-ketoglutarate. The mutation confers on IDH1\/2 the ability to convert alpha-ketoglutarate to (R)-2HG.<\/li>\n<li style=\"text-align: justify;\"><strong>Result<\/strong>: Addition of (R)-2HG is sufficient to transform cells. It does this by: (1) inhibiting TET2 (which acts to methylate histones) resulting in histone hypermethylation resulting in blockage of cell differentiation; and (2) synergizing the activity of the alpha-ketoglutarate target EGLN, which acts to inhibit (by marking for degradation) HIF-alpha, which is a transcription factor that inhibits proliferation and promotes differentiation.\n<div style=\"text-align: justify;\"><img decoding=\"async\" class=\"aligncenter\" 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\/><\/div>\n<\/li>\n<li style=\"text-align: justify;\"><strong>An implication<\/strong>: This adds detail to the dynamic interplay of the metabolic and epigenetic landscapes.<\/li>\n<\/ul>\n","protected":false},"excerpt":{"rendered":"<p>Concept: Oncometabolites. Also: Dynamic interplay of metabolome and epigenome. Source: News and Views\u00a0in Nature\u00a0(April 3, 2013) of a study published in Science. Background: It was already known that mutations in proteins involved in metabolism may be associated with cancer, but this is the first study to show that a metabolite may be sufficient for oncogenesis. [&hellip;]<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_monsterinsights_skip_tracking":false,"_monsterinsights_sitenote_active":false,"_monsterinsights_sitenote_note":"","_monsterinsights_sitenote_category":0,"_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":false,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_memberships_contains_paid_content":false,"footnotes":"","jetpack_publicize_message":"","jetpack_publicize_feature_enabled":true,"jetpack_social_post_already_shared":true,"jetpack_social_options":{"image_generator_settings":{"template":"highway","default_image_id":0,"font":"","enabled":false},"version":2},"jetpack_post_was_ever_published":false},"categories":[159,242,16,17],"tags":[],"metadata":[],"class_list":["post-2470","post","type-post","status-publish","format-standard","hentry","category-all-posts","category-evernote-entries","category-science","category-science-news"],"jetpack_publicize_connections":[],"jetpack_featured_media_url":"","jetpack-related-posts":[{"id":2513,"url":"https:\/\/thetravellerslastjourney.com\/shai\/2013\/04\/11\/science-news-pseudoenzymes\/","url_meta":{"origin":2470,"position":0},"title":"Science Review: Pseudoenzymes","author":"Pala","date":"April 11, 2013","format":false,"excerpt":"Concepts: Psudeoenzymes Source: A News Focus\u00a0piece in Science\u00a0(April 5, 2013). History: A 2002 study found that of 518 human protein kinases encoded in the DNA, about 10% lack at least one of three amino acids necessary for phosphate transfer. This was the first time the magnitude of the phenomenon was\u2026","rel":"","context":"In &quot;All Posts&quot;","block_context":{"text":"All Posts","link":"https:\/\/thetravellerslastjourney.com\/shai\/all-posts\/"},"img":{"alt_text":"","src":"","width":0,"height":0},"classes":[]},{"id":2476,"url":"https:\/\/thetravellerslastjourney.com\/shai\/2013\/04\/22\/science-review-pcsk9-assists-ldl-cholesterol-determined-cardiac-health-2\/","url_meta":{"origin":2470,"position":1},"title":"Science Review: PCSK9 assists LDL cholesterol determined cardiac health","author":"Pala","date":"April 22, 2013","format":false,"excerpt":"Concepts: PCSK9, and LDL cholesterol. Source: A News Feature\u00a0in Nature\u00a0(April 9, 2013). Background: PCSK9 circulates in the blood, binding to the LDL receptor on the surface of liver cells, taking them into the cell to be degraded. On the surface, LDL receptors capture LDL cholesterol to remove it from the\u2026","rel":"","context":"In &quot;All Posts&quot;","block_context":{"text":"All Posts","link":"https:\/\/thetravellerslastjourney.com\/shai\/all-posts\/"},"img":{"alt_text":"","src":"","width":0,"height":0},"classes":[]},{"id":2472,"url":"https:\/\/thetravellerslastjourney.com\/shai\/2013\/04\/07\/science-review-adaptive-diversification-2\/","url_meta":{"origin":2470,"position":2},"title":"Science Review: Adaptive diversification","author":"Pala","date":"April 7, 2013","format":false,"excerpt":"Concept: Adaptive diversification. Also: allopatric diversification; sympatric diversification; frequency-dependent selection. Source: An (original research) article published in PLoS Biology\u00a0(February 19, 2013) Background: A dichotomy of diversification follows depending on whether the\u00a0ancestral populations were geographically isolated from each other (allopatric diversification) or not (sympatric diversification). History: Same authors show that a\u2026","rel":"","context":"In &quot;All Posts&quot;","block_context":{"text":"All Posts","link":"https:\/\/thetravellerslastjourney.com\/shai\/all-posts\/"},"img":{"alt_text":"","src":"","width":0,"height":0},"classes":[]},{"id":2510,"url":"https:\/\/thetravellerslastjourney.com\/shai\/2013\/04\/29\/parallel-evolutionary-dynamics-of-adaptive-diversification\/","url_meta":{"origin":2470,"position":3},"title":"Science Review: Parallel evolutionary dynamics of adaptive diversification","author":"Pala","date":"April 29, 2013","format":false,"excerpt":"There is a Research Highlights piece (in Nat Rev Gen [Nature Review Genetics]) on a paper entitled Parallel evolutionary dynamics of adaptive diversification in Escherichia coli (in PLoS Biol), which studies the principle of\u00a0sympatric diversification, which is the \"organismal diversification or speciation that occurs without [...] geographical separation of [the]\u2026","rel":"","context":"In &quot;All Posts&quot;","block_context":{"text":"All Posts","link":"https:\/\/thetravellerslastjourney.com\/shai\/all-posts\/"},"img":{"alt_text":"","src":"","width":0,"height":0},"classes":[]},{"id":154,"url":"https:\/\/thetravellerslastjourney.com\/shai\/2013\/08\/17\/science-090813-paleoclimate-political-science-malaria-vaccine\/","url_meta":{"origin":2470,"position":4},"title":"Science 090813: Paleoclimate, political science, malaria vaccine","author":"Pala","date":"August 17, 2013","format":false,"excerpt":"Editorial notes: To understand the Meta paragraph below you need to read Shai's Priorities post where he discusses his own methodology for researching and acquiring knowledge. 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This letter will comprise a quasi-biographical form since that is the easiest medium for expressing and communicating my\u2026","rel":"","context":"In &quot;All Posts&quot;","block_context":{"text":"All Posts","link":"https:\/\/thetravellerslastjourney.com\/shai\/all-posts\/"},"img":{"alt_text":"","src":"","width":0,"height":0},"classes":[]}],"jetpack_sharing_enabled":true,"jetpack_shortlink":"https:\/\/wp.me\/padotI-DQ","_links":{"self":[{"href":"https:\/\/thetravellerslastjourney.com\/shai\/wp-json\/wp\/v2\/posts\/2470","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/thetravellerslastjourney.com\/shai\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/thetravellerslastjourney.com\/shai\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/thetravellerslastjourney.com\/shai\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/thetravellerslastjourney.com\/shai\/wp-json\/wp\/v2\/comments?post=2470"}],"version-history":[{"count":0,"href":"https:\/\/thetravellerslastjourney.com\/shai\/wp-json\/wp\/v2\/posts\/2470\/revisions"}],"wp:attachment":[{"href":"https:\/\/thetravellerslastjourney.com\/shai\/wp-json\/wp\/v2\/media?parent=2470"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/thetravellerslastjourney.com\/shai\/wp-json\/wp\/v2\/categories?post=2470"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/thetravellerslastjourney.com\/shai\/wp-json\/wp\/v2\/tags?post=2470"},{"taxonomy":"metadata","embeddable":true,"href":"https:\/\/thetravellerslastjourney.com\/shai\/wp-json\/wp\/v2\/metadata?post=2470"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}