Cyclin D2 is a GATA4 cofactor in cardiogenesis

Yamak, Abir; Latinkic, Branko; Dali, Rola; Temsah, Rana M.; Nemer, Mona

doi:10.1073/pnas.1312993111

Cited by 33 publications

(33 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…6). GATA4 and TBX5 interact physically to activate gene expression synergistically in the heart (2), and multiple Gata4 transcriptional targets have been identified in the heart (1,4,5,7,22,64). Recent studies have indicated that GATA4 and TBX5 are essential for each other's transcriptional fidelity in the control of cardiac gene regulatory networks in mouse and human models (65,66).…”

Section: In Control Gli1mentioning

confidence: 99%

Gata4 potentiates second heart field proliferation and Hedgehog signaling for cardiac septation

Zhou

Liu

Xiang

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

GATA4, an essential cardiogenic transcription factor, provides a model for dominant transcription factor mutations in human disease. Dominant GATA4 mutations cause congenital heart disease (CHD), specifically atrial and atrioventricular septal defects (ASDs and AVSDs). We found that second heart field (SHF)-specific Gata4 heterozygote embryos recapitulated the AVSDs observed in germline Gata4 heterozygote embryos. A proliferation defect of SHF atrial septum progenitors and hypoplasia of the dorsal mesenchymal protrusion, rather than anlage of the atrioventricular septum, were observed in this model. Knockdown of the cell-cycle repressor phosphatase and tensin homolog (Pten) restored cell-cycle progression and rescued the AVSDs. Gata4 mutants also demonstrated Hedgehog (Hh) signaling defects. Gata4 acts directly upstream of Hh components: Gata4 activated a cisregulatory element at Gli1 in vitro and occupied the element in vivo. Remarkably, SHF-specific constitutive Hh signaling activation rescued AVSDs in Gata4 SHF-specific heterozygous knockout embryos. Pten expression was unchanged in Smoothened mutants, and Hh pathway genes were unchanged in Pten mutants, suggesting pathway independence. Thus, both the cell-cycle and Hh-signaling defects caused by dominant Gata4 mutations were required for CHD pathogenesis, suggesting a combinatorial model of disease causation by transcription factor haploinsufficiency.Gata4 | ASDs | Hedgehog signaling | second heart field | cell cycle

show abstract

Section: In Control Gli1mentioning

confidence: 99%

Gata4 potentiates second heart field proliferation and Hedgehog signaling for cardiac septation

Zhou

Liu

Xiang

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…1). A recent work uncovered a role for cyclin D2 as a cardiogenic coactivator of GATA4 and suggests a paradigm for cell-specific effects of cyclin D proteins (Yamak et al, 2014).…”

Section: Cyclin Dmentioning

confidence: 99%

Cdk5 activity in the brain – multiple paths of regulation

Shah

Lahiri

2014

Journal of Cell Science

169

126

View full text Add to dashboard Cite

Cyclin dependent kinase-5 (Cdk5), a family member of the cyclindependent kinases, plays a pivotal role in the central nervous system. During embryogenesis, Cdk5 is indispensable for brain development and, in the adult brain, it is essential for numerous neuronal processes, including higher cognitive functions such as learning and memory formation. However, Cdk5 activity becomes deregulated in several neurological disorders, such as Alzheimer's disease, Parkinson's disease and Huntington's disease, which leads to neurotoxicity. Therefore, precise control over Cdk5 activity is essential for its physiological functions. This Commentary covers the various mechanisms of Cdk5 regulation, including several recently identified protein activators and inhibitors of Cdk5 that control its activity in normal and diseased brains. We also discuss the autoregulatory activity of Cdk5 and its regulation at the transcriptional, post-transcriptional and post-translational levels. We finally highlight physiological and pathological roles of Cdk5 in the brain. Specific modulation of these protein regulators is expected to provide alternative strategies for the development of effective therapeutic interventions that are triggered by deregulation of Cdk5.

show abstract

“…In Vitro Pulldown Assay-Production of the GST-TBX5a and MBP-NKX2.5 constructs (where MBP is maltose-binding protein) and the pulldown assays were done as described previously (24).…”

Section: Methodsmentioning

confidence: 99%

Novel Exons in the Tbx5 Gene Locus Generate Protein Isoforms with Distinct Expression Domains and Function

Yamak

Georges

Sheikh-Hassani

et al. 2015

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Background: TBX5 is the causative gene for Holt-Oram syndrome (HOS), characterized by forelimb abnormalities and heart problems; however, 30% of patients have no mutation in known exons. Results: TBX5 isoforms derived from novel exons have distinct expression domains and function. Conclusion: Alternative splicing regulates TBX5 function in heart and limb. Significance: This is relevant for human mutational screening and for understanding TBX5 function.

show abstract

Cyclin D2 is a GATA4 cofactor in cardiogenesis

Cited by 33 publications

References 54 publications

Gata4 potentiates second heart field proliferation and Hedgehog signaling for cardiac septation

Gata4 potentiates second heart field proliferation and Hedgehog signaling for cardiac septation

Cdk5 activity in the brain – multiple paths of regulation

Novel Exons in the Tbx5 Gene Locus Generate Protein Isoforms with Distinct Expression Domains and Function

Contact Info

Product

Resources

About