TEAD1
Transcriptional enhancer factor TEF-1 (NTEF-1) (Protein GT-IIC) (TEA domain family member 1) (TEAD-1) (Transcription factor 13) (TCF-13) [TCF13] [TEF1]
Publications[править]
The distribution of allele and genotype frequencies of Alu(I/D)-polymorphic sites in PLAT (TPA25), PKHD1L1 (Yb8AC702), STK38L (Ya5ac2145) и TEAD1 (Ya5ac2013) genes was first characterized in the ethnically homogeneous group (Tatars from the Republic of Bashkortostan, Russia), and was established (found) the association of each gene polymorphism with age. The study group consisted of 1580 unrelated individuals aged between 21 and 109 years, including 204 long-livers. It was found that STK38L*I/D genotype had positive association with longevity in the total group (OR=1,016, p=0,034). Long-lived women had a high probability of detection of PKHD1L1*I/I (OR=1,289, p=0,009), PLAT*D/D (OR=1,175, p=0,016) and TEAD1*I/I (OR=1,047, p=0,042) genotypes. PKHD1L1*I/D genotype was a significant factor in providing of male longevity (OR=1,713, p=0,030). Therefore, age-dependent changes in genotype frequencies are specific for each studied gene.
MeSH Terms
- Adult
- Aged
- Aged, 80 and over
- Alu Elements
- DNA-Binding Proteins
- Ethnic Groups
- Female
- Gene Frequency
- Humans
- Longevity
- Male
- Middle Aged
- Nuclear Proteins
- Polymorphism, Genetic
- Protein-Serine-Threonine Kinases
- Receptors, Cell Surface
- Russia
- Transcription Factors
Keywords
- Alu-I/D polymorphism
- PKHD1L1
- STK38L
- TEAD1
- association analysis
- gene instability
- genes of PLAT
- lifespan
- longevity
- tatars ethnic group
Binding of the transcriptional co-activator YAP with the transcription factor TEAD stimulates growth of the heart and other organs. YAP overexpression potently stimulates fetal cardiomyocyte (CM) proliferation, but YAP's mitogenic potency declines postnatally. While investigating factors that limit YAP's postnatal mitogenic activity, we found that the CM-enriched TEAD1 binding protein VGLL4 inhibits CM proliferation by inhibiting TEAD1-YAP interaction and by targeting TEAD1 for degradation. Importantly, VGLL4 acetylation at lysine 225 negatively regulated its binding to TEAD1. This developmentally regulated acetylation event critically governs postnatal heart growth, since overexpression of an acetylation-refractory VGLL4 mutant enhanced TEAD1 degradation, limited neonatal CM proliferation, and caused CM necrosis. Our study defines an acetylation-mediated, VGLL4-dependent switch that regulates TEAD stability and YAP-TEAD activity. These insights may improve targeted modulation of TEAD-YAP activity in applications from cardiac regeneration to cancer.
MeSH Terms
- Acetylation
- Adaptor Proteins, Signal Transducing
- Aging
- Amino Acid Sequence
- Animals
- Animals, Newborn
- Cell Cycle Proteins
- Cell Proliferation
- DNA-Binding Proteins
- Heart
- Heart Failure
- Humans
- Phosphoproteins
- Protein Binding
- Protein Domains
- Protein Stability
- Protein-Serine-Threonine Kinases
- Rats, Wistar
- Signal Transduction
- Transcription Factors
Keywords
- Hippo-YAP pathway
- TEAD1
- VGLL4
- acetylation
- cardiac
- cardiomyocyte
- degradation
- necrosis
- proliferation