Glutaminase Affects the Transcriptional Activity of Peroxisome Proliferator-Activated Receptor γ (PPARγ) via Direct Interaction

Biochemistry ◽  
2018 ◽  
Vol 57 (44) ◽  
pp. 6293-6307 ◽  
Author(s):  
Carolina Aparecida de Guzzi Cassago ◽  
Marília Meira Dias ◽  
Matheus Pinto Pinheiro ◽  
Camila Cristina Pasquali ◽  
Alliny Cristiny Silva Bastos ◽  
...  
Keyword(s):  
Transcriptional Activity ◽  
Direct Interaction ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

scholarly journals Regulation of the Transcriptional Activity of the Peroxisome Proliferator-activated Receptor α by Phosphorylation of a Ligand-independenttrans-Activating Domain

1999 ◽  
Vol 274 (15) ◽  
pp. 10505-10510 ◽  
Author(s):  
Cristiana E. Juge-Aubry ◽  
Eva Hammar ◽  
Catherine Siegrist-Kaiser ◽  
Agnès Pernin ◽  
Akira Takeshita ◽  
...  
Keyword(s):  
Transcriptional Activity ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

scholarly journals Dietary Modulation of Inflammation-Induced Colorectal Cancer through PPARγ

PPAR Research ◽  
2009 ◽  
Vol 2009 ◽  
pp. 1-9 ◽  
Author(s):  
Ashlee B. Carter ◽  
Sarah A. Misyak ◽  
Raquel Hontecillas ◽  
Josep Bassaganya-Riera
Keyword(s):  
Colorectal Cancer ◽  
Immune Responses ◽  
Transcriptional Activity ◽  
Inflammatory Diseases ◽  
Risk Groups ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Naturally Occurring ◽  
Increased Risk ◽  
Orally Active

Mounting evidence suggests that the risk of developing colorectal cancer (CRC) is dramatically increased for patients with chronic inflammatory diseases. For instance, patients with Crohn's Disease (CD) or Ulcerative Colitis (UC) have a 12–20% increased risk for developing CRC. Preventive strategies utilizing nontoxic natural compounds that modulate immune responses could be successful in the suppression of inflammation-driven colorectal cancer in high-risk groups. The increase of peroxisome proliferator-activated receptor-γ(PPAR-γ) expression and its transcriptional activity has been identified as a target for anti-inflammatory efforts, and the suppression of inflammation-driven colon cancer. PPARγdown-modulates inflammation and elicits antiproliferative and proapoptotic actions in epithelial cells. All of which may decrease the risk for inflammation-induced CRC. This review will focus on the use of orally active, naturally occurring chemopreventive approaches against inflammation-induced CRC that target PPARγand therefore down-modulate inflammation.

Peroxisomal bifunctional enzyme binds and activates the activationfunction-1 region of the peroxisome proliferator-activated receptor α

2001 ◽  
Vol 353 (2) ◽  
pp. 253-258 ◽  
Author(s):  
Cristiana E. JUGE-AUBRY ◽  
Stéphane KUENZLI ◽  
Jean-Charles SANCHEZ ◽  
Denis HOCHSTRASSER ◽  
Christoph A. MEIER
Keyword(s):  
Amino Acids ◽  
Transcriptional Activity ◽  
Hormone Receptors ◽  
Affinity Purification ◽  
Fold Increase ◽  
Activation Function ◽  
Bifunctional Enzyme ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
Peroxisome Proliferator Activated Receptor

The transcriptional activity of peroxisome proliferator-activated receptors (PPARs), and of nuclear hormone receptors in general, is subject to modulation by cofactors. However, most currently known co-activating proteins interact in a ligand-dependent manner with the C-terminal ligand-regulated activation function (AF)-2 domain of nuclear receptors. Since PPARα exhibits a strong constitutive transactivating function contained within an N-terminal AF-1 region, it can be speculated that a different set of cofactors might interact with this region of PPARs. An affinity purification approach was used to identify the peroxisomal enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase (bifunctional enzyme, BFE) as a protein which strongly and specifically interacted with the N-terminal 92 amino acids of PPARα. ProteinŐprotein interaction assays with the cloned BFE confirmed this interaction, which could be mapped to amino acids 307Ő514 of the BFE and the N-terminal 70 amino acids of PPARα. Moreover, transient transfection experiments in hepatoma cells revealed a 2.2-fold increase in the basal and ligand-stimulated transcriptional activity of PPARα in the presence of BFE. This stimulatory effect is preferentially observed for the PPARα isoform and it is significantly stronger (4.8-fold) in non-hepatic cells, which presumably express lower levels of endogenous BFE. Hence, the BFE represents the first known cofactor capable of activating the AF-1 domain of PPAR without requiring additional regions of this receptor. These data are compatible with a model whereby the PPAR-regulated BFE is able to modulate its own expression through an enhancement of the activity of PPARα, representing a novel peroxisomalŐnuclear feed-forward regulatory loop.

scholarly journals The Ribosomal Protein rpL11 Associates with and Inhibits the Transcriptional Activity of Peroxisome Proliferator-Activated Receptor-α

2005 ◽  
Vol 89 (2) ◽  
pp. 535-546 ◽  
Author(s):  
Joshua P. Gray ◽  
John W. Davis ◽  
Lakshmi Gopinathan ◽  
Tara L. Leas ◽  
Courtney A. Nugent ◽  
...  
Keyword(s):  
Ribosomal Protein ◽  
Transcriptional Activity ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

scholarly journals Homeostatic levels of SRC-2 and SRC-3 promote early human adipogenesis

2011 ◽  
Vol 192 (1) ◽  
pp. 55-67 ◽  
Author(s):  
Sean M. Hartig ◽  
Bin He ◽  
Weiwen Long ◽  
Benjamin M. Buehrer ◽  
Michael A. Mancini
Keyword(s):  
Transcriptional Activity ◽  
Adipocyte Differentiation ◽  
Cellular Heterogeneity ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Human Adipocyte ◽  
Lipogenic Gene ◽  
Protein Levels ◽  
High Content Analysis ◽  
Early Human

The related coactivators SRC-2 and SRC-3 interact with peroxisome proliferator activated receptor γ (PPARγ) to coordinate transcriptional circuits to promote adipogenesis. To identify potential coactivator redundancy during human adipogenesis at single cell resolution, we used high content analysis to quantify links between PPARγ, SRC-2, SRC-3, and lipogenesis. Because we detected robust increases and significant cell–cell heterogeneity in PPARγ and lipogenesis, without changes in SRC-2 or SRC-3, we hypothesized that permissive coregulator levels comprise a necessary adipogenic equilibrium. We probed this equilibrium by down-regulating SRC-2 and SRC-3 while simultaneously quantifying PPARγ. Individual or joint knockdown equally inhibits lipid accumulation by preventing lipogenic gene engagement, without affecting PPARγ protein levels. Supporting dominant, pro-adipogenic roles for SRC-2 and SRC-3, SRC-1 knockdown does not affect adipogenesis. SRC-2 and SRC-3 knockdown increases the proportion of cells in a PPARγhi/lipidlo state while increasing phospho-PPARγ–S114, an inhibitor of PPARγ transcriptional activity and adipogenesis. Together, we demonstrate that SRC-2 and SRC-3 concomitantly promote human adipocyte differentiation by attenuating phospho-PPARγ–S114 and modulating PPARγ cellular heterogeneity.

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