Casillas AL, et al. (2021) Direct phosphorylation and stabilization of HIF-1α by PIM1 kinase drives angiogenesis in solid tumors. Oncogene 34211090

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T455-p - HIF1A (human) ▲

Modsite: LAMsPLPtAEtPkPL SwissProt Entrez-Gene Orthologous residues HIF1A (human): T455‑p, HIF1A (mouse): S454‑p, HIF1A (rat): A454‑p Characterization Methods used to characterize site in vivo:  immunoassay, mass spectrometry, mass spectrometry (in vitro), mutation of modification site, phospho-antibody, western blotting Disease tissue studied:  colorectal cancer, colorectal carcinoma, lung cancer, non-small cell lung cancer, non-small cell lung adenocarcinoma, prostate cancer Relevant cell lines - cell types - tissues:  A549 (pulmonary), C4-2B (prostate cell), HCT116 (intestinal), HEK293T (epithelial), PC3 (prostate cell), RKO (intestinal), SW620 (intestinal) Cellular systems studied:  cell lines Species studied:  human Enzymes shown to modify site in vitro:  Type Enzyme KINASE Pim1 (human) Upstream Regulation Potential in vivo enzymes for site:  Type Enzyme Evidence Notes KINASE Pim1 (human) transfection of wild-type enzyme, pharmacological inhibitor of upstream enzyme, co-immunoprecipitation, siRNA inhibition of enzyme Treatments, proteins and their effect on site modification:  Treatments Referenced Treatments Manipulated Protein Referenced Protein Effect Notes PIM447 decrease AZD1208 decrease hypoxia increase siRNA hypoxia inhibit treatment-induced increase Pim1 siRNA siRNA decrease PIM1 siRNA Downstream Regulation Effect of modification (function):  molecular association, regulation, protein stabilization, ubiquitination Effect of modification (process):  carcinogenesis, induced, cell growth, induced, transcription, induced Modification regulates interactions with:  Interacting molecule Interacting domains Effect Consequences (function) Consequences (process) Detection assays EGLN1 (human) Disrupts co-immunoprecipitation Comments:  inhibits ubiquitination

S435-p - HIF2A (human) ▲

Modsite: GKAILPPsQPWATEL SwissProt Entrez-Gene Orthologous residues HIF2A (human): S435‑p, HIF2A (mouse): G435‑p, HIF2A (rat): G435‑p Characterization Methods used to characterize site in vivo:  immunoassay, mass spectrometry, mass spectrometry (in vitro), mutation of modification site, phospho-antibody, western blotting Disease tissue studied:  colorectal cancer, colorectal carcinoma, lung cancer, non-small cell lung cancer, non-small cell lung adenocarcinoma, prostate cancer Relevant cell lines - cell types - tissues:  A549 (pulmonary), C4-2B (prostate cell), HCT116 (intestinal), HEK293T (epithelial), PC3 (prostate cell), RKO (intestinal), SW620 (intestinal) Cellular systems studied:  cell lines Species studied:  human Upstream Regulation Potential in vivo enzymes for site:  Type Enzyme Evidence Notes KINASE Pim1 (human) transfection of wild-type enzyme, pharmacological inhibitor of upstream enzyme, co-immunoprecipitation, siRNA inhibition of enzyme Treatments, proteins and their effect on site modification:  Treatments Referenced Treatments Manipulated Protein Referenced Protein Effect Notes PIM447 decrease AZD1208 decrease hypoxia increase siRNA hypoxia inhibit treatment-induced increase Pim1 siRNA siRNA decrease PIM1 siRNA Downstream Regulation Effect of modification (function):  molecular association, regulation, protein stabilization, ubiquitination Effect of modification (process):  carcinogenesis, induced, cell growth, induced, transcription, induced Modification regulates interactions with:  Interacting molecule Interacting domains Effect Consequences (function) Consequences (process) Detection assays EGLN1 (human) Disrupts co-immunoprecipitation Comments:  inhibits ubiquitination