A HIf1α regulatory loop links hypoxia and mitochondrial signals in pheochromocytomas

Dahia, PLM; Ross, KN; Wright, ME; Hayashida, CY; Santagata, S; Barontini, M; Kung, AL; Sanso, G; Powers, JF; Tischler, AS; Hodin, R; Heitritter, S; Moore, F; Dluhy, R; Sosa, JA; Ocal, IT; Benn, DE; Marsh, DJ; Robinson, BG; Schneider, K; Garber, J; Arum, SM; Korbonits, M; Grossman, A; Pigny, P; Toledo, SPA; Nose, V; Li, C; Stiles, CD

A HIf1α regulatory loop links hypoxia and mitochondrial signals in pheochromocytomas

Dahia, PLM Ross, KN Wright, ME Hayashida, CY Santagata, S Barontini, M Kung, AL Sanso, G Powers, JF Tischler, AS Hodin, R Heitritter, S Moore, F Dluhy, R Sosa, JA Ocal, IT Benn, DE Marsh, DJ

Robinson, BG Schneider, K Garber, J Arum, SM Korbonits, M Grossman, A Pigny, P Toledo, SPA Nose, V Li, C Stiles, CD

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Publication Type:: Journal Article
Citation:: PLoS Genetics, 2005, 1 (1), pp. 0072 - 0080
Issue Date:: 2005-07-01

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Field	Value	Language
dc.contributor.author	Dahia, PLM	en_US
dc.contributor.author	Ross, KN	en_US
dc.contributor.author	Wright, ME	en_US
dc.contributor.author	Hayashida, CY	en_US
dc.contributor.author	Santagata, S	en_US
dc.contributor.author	Barontini, M	en_US
dc.contributor.author	Kung, AL	en_US
dc.contributor.author	Sanso, G	en_US
dc.contributor.author	Powers, JF	en_US
dc.contributor.author	Tischler, AS	en_US
dc.contributor.author	Hodin, R	en_US
dc.contributor.author	Heitritter, S	en_US
dc.contributor.author	Moore, F	en_US
dc.contributor.author	Dluhy, R	en_US
dc.contributor.author	Sosa, JA	en_US
dc.contributor.author	Ocal, IT	en_US
dc.contributor.author	Benn, DE	en_US
dc.contributor.author	Marsh, DJ https://orcid.org/0000-0001-5899-4931	en_US
dc.contributor.author	Robinson, BG	en_US
dc.contributor.author	Schneider, K	en_US
dc.contributor.author	Garber, J	en_US
dc.contributor.author	Arum, SM	en_US
dc.contributor.author	Korbonits, M	en_US
dc.contributor.author	Grossman, A	en_US
dc.contributor.author	Pigny, P	en_US
dc.contributor.author	Toledo, SPA	en_US
dc.contributor.author	Nose, V	en_US
dc.contributor.author	Li, C	en_US
dc.contributor.author	Stiles, CD	en_US
dc.date.accessioned	2020-04-23T14:11:16Z
dc.date.available	2005-05-09	en_US
dc.date.available	2020-04-23T14:11:16Z
dc.date.issued	2005-07-01	en_US
dc.identifier.citation	PLoS Genetics, 2005, 1 (1), pp. 0072 - 0080	en_US
dc.identifier.issn	1553-7390	en_US
dc.identifier.uri	http://hdl.handle.net/10453/140221
dc.description.abstract	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 HIF1a. These findings explain the shared features of pheochromocytomas with VHL and SDH mutations and suggest an additional mechanism for increased HIF1a activity in tumors. © 2005 Dahia et al.	en_US
dc.relation.ispartof	PLoS Genetics	en_US
dc.relation.isbasedon	10.1371/journal.pgen.0010008	en_US
dc.rights	info:eu-repo/semantics/openAccess
dc.subject.classification	Developmental Biology	en_US
dc.title	A HIf1α regulatory loop links hypoxia and mitochondrial signals in pheochromocytomas	en_US
dc.type	Journal Article
utslib.citation.volume	1	en_US
utslib.for	0604 Genetics	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
utslib.copyright.status	open_access	*
pubs.issue	1	en_US
pubs.publication-status	Published	en_US
pubs.volume	1	en_US

Abstract:

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 HIF1a. These findings explain the shared features of pheochromocytomas with VHL and SDH mutations and suggest an additional mechanism for increased HIF1a activity in tumors. © 2005 Dahia et al.

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http://hdl.handle.net/10453/140221