scholarly journals The Role of Cytoplasmic Polyadenylation Element Binding Protein 2 Alternative Splicing in Chronic Hypoxia

2021 ◽  
Vol 35 (S1) ◽  
Author(s):  
Emily Mayo ◽  
Margaret Park
Keyword(s):  
Alternative Splicing ◽  
Chronic Hypoxia ◽  
Binding Protein ◽  
Cytoplasmic Polyadenylation ◽  
Element Binding Protein

scholarly journals The role of cytosolic polyadenylation element binding protein 2 alternative splicing in hypoxia

2020 ◽  
Author(s):  
Emily M. Mayo ◽  
Shaun C. Stevens ◽  
Anika N. Ali ◽  
Christina J. Moss ◽  
Sean P. Lund ◽  
...  
Keyword(s):  
Chronic Hypoxia ◽  
Binding Protein ◽  
Hypoxia Inducible Factor ◽  
Inhibitory Effect ◽  
Initiation Factor ◽  
Cytoplasmic Polyadenylation ◽  
Translational Repressor ◽  
Hypoxia Exposure ◽  
Element Binding Protein ◽  
Translational Activator

AbstractHIF1 (Hypoxia-inducible Factor 1) is a transcription factor that plays a crucial role in the hypoxia stress response. Its primary function is to return the cell to its homeostatic state following oxygen deprivation. However, chronic hypoxia exposure can cause irreversible physiological changes that can lead to pulmonary hypertension (PH) and the need for therapeutics to ameliorate these conditions is great and unmet. Previous studies in our lab have demonstrated that CPEB2 (cytoplasmic polyadenylation element binding protein 2) is a translational repressor of one of the HIF1 subunits: HIF1α. Our lab demonstrated that the alternatively spliced CPEB2A isoform of CPEB2 is a repressor of translation, while the CPEB2B isoform is a translational activator of HIF1α during hypoxia, suggesting a major regulatory role for CPEB2 AS in the pulmonary hypoxic response. Although it is well established that during hypoxia, HIF1α levels are dramatically upregulated due to a decrease in the degradation of this factor, we propose that during chronic hypoxia, the expression of HIF1α is maintained via a translational mechanism, likely alongside a decrease in proteolytic degradation. In this study we demonstrate that depletion of the CPEB2B splice isoform has an inhibitory effect on the translation of nascent HIF1α protein during chronic hypoxia, but not the acute phase. We further demonstrate that this pathway is dependent on the initiation factor eIF3H. Finally, we show data which indicate that CPEB2A and CPEB2B bind differentially to cytoplasmic polyadenylation element consensus sequences depending on surrounding sequence context. These findings are important, since they provide evidence for potential of CPEB2 to act as a therapeutic target for treating chronic hypoxia-related pulmonary diseases.

scholarly journals Serine/Arginine–Rich Splicing Factor 3 Modulates the Alternative Splicing of Cytoplasmic Polyadenylation Element Binding Protein 2

2019 ◽  
Vol 17 (9) ◽  
pp. 1920-1930 ◽  
Author(s):  
James T. DeLigio ◽  
Shaun C. Stevens ◽  
Gina S. Nazario-Muñoz ◽  
H. Patrick MacKnight ◽  
Keli K. Doe ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Binding Protein ◽  
Splicing Factor ◽  
Cytoplasmic Polyadenylation ◽  
Element Binding Protein

scholarly journals p300/cAMP-response-element-binding-protein ('CREB')-binding protein (CBP) modulates co-operation between myocyte enhancer factor 2A (MEF2A) and thyroid hormone receptor-retinoid X receptor

2003 ◽  
Vol 369 (3) ◽  
pp. 477-484 ◽  
Author(s):  
Antonio De LUCA ◽  
Anna SEVERINO ◽  
Paola De PAOLIS ◽  
Giuliano COTTONE ◽  
Luca De LUCA ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Binding Protein ◽  
Camp Response Element Binding ◽  
Creb Binding Protein ◽  
Camp Response Element ◽  
Response Element ◽  
Adenovirus E1a ◽  
Element Binding Protein ◽  
Enhancer Factor

Thyroid hormone receptors (TRs) and members of the myocyte enhancer factor 2 (MEF2) family are involved in the regulation of muscle-specific gene expression during myogenesis. Physical interaction between these two factors is required to synergistically activate gene transcription. p300/cAMP-response-element-binding-protein ('CREB')-binding protein (CBP) interacting with transcription factors is able to increase their activity on target gene promoters. We investigated the role of p300 in regulating the TR—MEF2A complex. To this end, we mapped the regions of these proteins involved in physical interactions and we evaluated the expression of a chloramphenicol acetyltransferase (CAT) reporter gene in U2OS cells under control of the α-myosin heavy chain promoter containing the thyroid hormone response element (TRE). Our results suggested a role of p300/CBP in mediating the transactivation effects of the TR—retenoid X receptor (RxR)—MEF2A complex. Our findings showed that the same C-terminal portion of p300 binds the N-terminal domains of both TR and MEF2A, and our in vivo studies demonstrated that TR, MEF2A and p300 form a ternary complex. Moreover, by the use of CAT assays, we demonstrated that adenovirus E1A inhibits activation of transcription by TR—RxR—MEF2A—p300 but not by TR—RxR—MEF2A. Our data suggested that p300 can bind and modulate the activity of TR—RxR—MEF2A at TRE. In addition, it is speculated that p300 might modulate the activity of the TR—RxR—MEF2A complex by recruiting a hypothetical endogenous inhibitor which may act like adenovirus E1A.

Corrigendum to “Reversion of hepatic steatosis by exercise training in obese mice: The role of sterol regulatory element-binding protein-1c” [Life Sci. 91(11–12) (2012) 395–401]

Life Sciences ◽  
2016 ◽  
Vol 152 ◽  
pp. 178-179
Author(s):  
Dennys E. Cintra ◽  
Eduardo R. Ropelle ◽  
Marcelo F. Vitto ◽  
Thais F. Luciano ◽  
Daniela R. Souza ◽  
...  
Keyword(s):  
Exercise Training ◽  
Hepatic Steatosis ◽  
Binding Protein ◽  
Regulatory Element ◽  
Obese Mice ◽  
Element Binding Protein ◽  
Sterol Regulatory Element
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