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A HIF1α Regulatory Loop Links Hypoxia and Mitochondrial Signals in Pheochromocytomas
Pheochromocytomas are neural crest–derived tumors that arise from inherited or sporadic mutations in at least six independent genes. The proteins encoded by these multiple genes regulate distinct functions. We show here a functional link between tumors with VHL mutations and those with disruption of...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2005
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1183527/ https://www.ncbi.nlm.nih.gov/pubmed/16103922 http://dx.doi.org/10.1371/journal.pgen.0010008 |
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author | Dahia, Patricia L. M Ross, Ken N Wright, Matthew E Hayashida, César Y Santagata, Sandro Barontini, Marta Kung, Andrew L Sanso, Gabriela Powers, James F Tischler, Arthur S Hodin, Richard Heitritter, Shannon Moore, Francis Dluhy, Robert Sosa, Julie Ann Ocal, I. Tolgay Benn, Diana E Marsh, Deborah J Robinson, Bruce G Schneider, Katherine Garber, Judy Arum, Seth M Korbonits, Márta Grossman, Ashley Pigny, Pascal Toledo, Sérgio P. A Nosé, Vania Li, Cheng Stiles, Charles D |
author_facet | Dahia, Patricia L. M Ross, Ken N Wright, Matthew E Hayashida, César Y Santagata, Sandro Barontini, Marta Kung, Andrew L Sanso, Gabriela Powers, James F Tischler, Arthur S Hodin, Richard Heitritter, Shannon Moore, Francis Dluhy, Robert Sosa, Julie Ann Ocal, I. Tolgay Benn, Diana E Marsh, Deborah J Robinson, Bruce G Schneider, Katherine Garber, Judy Arum, Seth M Korbonits, Márta Grossman, Ashley Pigny, Pascal Toledo, Sérgio P. A Nosé, Vania Li, Cheng Stiles, Charles D |
author_sort | Dahia, Patricia L. M |
collection | PubMed |
description | Pheochromocytomas are neural crest–derived tumors that arise from inherited or sporadic mutations in at least six independent genes. The proteins encoded by these multiple genes regulate distinct functions. We show here a functional link between tumors with VHL mutations and those with disruption of the genes encoding for succinate dehydrogenase (SDH) subunits B (SDHB) and D (SDHD). A transcription profile of reduced oxidoreductase is detected in all three of these tumor types, together with an angiogenesis/hypoxia profile typical of VHL dysfunction. The oxidoreductase defect, not previously detected in VHL-null tumors, is explained by suppression of the SDHB protein, a component of mitochondrial complex II. The decrease in SDHB is also noted in tumors with SDHD mutations. Gain-of-function and loss-of-function analyses show that the link between hypoxia signals (via VHL) and mitochondrial signals (via SDH) is mediated by HIF1α. These findings explain the shared features of pheochromocytomas with VHL and SDH mutations and suggest an additional mechanism for increased HIF1α activity in tumors. |
format | Text |
id | pubmed-1183527 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2005 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-11835272005-08-15 A HIF1α Regulatory Loop Links Hypoxia and Mitochondrial Signals in Pheochromocytomas Dahia, Patricia L. M Ross, Ken N Wright, Matthew E Hayashida, César Y Santagata, Sandro Barontini, Marta Kung, Andrew L Sanso, Gabriela Powers, James F Tischler, Arthur S Hodin, Richard Heitritter, Shannon Moore, Francis Dluhy, Robert Sosa, Julie Ann Ocal, I. Tolgay Benn, Diana E Marsh, Deborah J Robinson, Bruce G Schneider, Katherine Garber, Judy Arum, Seth M Korbonits, Márta Grossman, Ashley Pigny, Pascal Toledo, Sérgio P. A Nosé, Vania Li, Cheng Stiles, Charles D PLoS Genet Research Article Pheochromocytomas are neural crest–derived tumors that arise from inherited or sporadic mutations in at least six independent genes. The proteins encoded by these multiple genes regulate distinct functions. We show here a functional link between tumors with VHL mutations and those with disruption of the genes encoding for succinate dehydrogenase (SDH) subunits B (SDHB) and D (SDHD). A transcription profile of reduced oxidoreductase is detected in all three of these tumor types, together with an angiogenesis/hypoxia profile typical of VHL dysfunction. The oxidoreductase defect, not previously detected in VHL-null tumors, is explained by suppression of the SDHB protein, a component of mitochondrial complex II. The decrease in SDHB is also noted in tumors with SDHD mutations. Gain-of-function and loss-of-function analyses show that the link between hypoxia signals (via VHL) and mitochondrial signals (via SDH) is mediated by HIF1α. These findings explain the shared features of pheochromocytomas with VHL and SDH mutations and suggest an additional mechanism for increased HIF1α activity in tumors. Public Library of Science 2005-07 2005-07-25 /pmc/articles/PMC1183527/ /pubmed/16103922 http://dx.doi.org/10.1371/journal.pgen.0010008 Text en Copyright: © 2005 Dahia et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Dahia, Patricia L. M Ross, Ken N Wright, Matthew E Hayashida, César Y Santagata, Sandro Barontini, Marta Kung, Andrew L Sanso, Gabriela Powers, James F Tischler, Arthur S Hodin, Richard Heitritter, Shannon Moore, Francis Dluhy, Robert Sosa, Julie Ann Ocal, I. Tolgay Benn, Diana E Marsh, Deborah J Robinson, Bruce G Schneider, Katherine Garber, Judy Arum, Seth M Korbonits, Márta Grossman, Ashley Pigny, Pascal Toledo, Sérgio P. A Nosé, Vania Li, Cheng Stiles, Charles D A HIF1α Regulatory Loop Links Hypoxia and Mitochondrial Signals in Pheochromocytomas |
title | A HIF1α Regulatory Loop Links Hypoxia and Mitochondrial Signals in Pheochromocytomas |
title_full | A HIF1α Regulatory Loop Links Hypoxia and Mitochondrial Signals in Pheochromocytomas |
title_fullStr | A HIF1α Regulatory Loop Links Hypoxia and Mitochondrial Signals in Pheochromocytomas |
title_full_unstemmed | A HIF1α Regulatory Loop Links Hypoxia and Mitochondrial Signals in Pheochromocytomas |
title_short | A HIF1α Regulatory Loop Links Hypoxia and Mitochondrial Signals in Pheochromocytomas |
title_sort | hif1α regulatory loop links hypoxia and mitochondrial signals in pheochromocytomas |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1183527/ https://www.ncbi.nlm.nih.gov/pubmed/16103922 http://dx.doi.org/10.1371/journal.pgen.0010008 |
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