Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P23193 (transcription elongation factor)
 739 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aging and reproduction are two defining features of our life. Historically, research has focused on the well-documented decline in reproductive capacity that accompanies old age, especially with increasing maternal age in humans. However, recent experiments in model organisms such as worms, flies, and mice have shown that a dialogue in the opposite direction may be widely prevalent, and that signals from reproductive tissues have a significant effect on the rate of aging of organisms. This pathway has been described in considerable detail in the nematode Caenorhabditis elegans. Molecular genetic studies suggest that signals from the germline control a network of transcriptional regulators that function in the intestine to influence longevity. This network includes conserved, longevity-promoting Forkhead Box (FOX) family transcription factors such as DAF-16/FOXO and PHA-4/FOXA, nuclear hormone receptors, as well as a transcription elongation factor, TCER-1/TCERG1. Genomic and targeted molecular analyses have revealed that these transcription factors modulate autophagy, lipid metabolism, and possibly other cellular processes to increase the length of the animal's life. This review aims to provide an overview of the current knowledge on the genetic mechanism that underlies the reproductive control of aging with particular focus on the transcriptional regulators that constitute the main molecular players in this longevity pathway.
Genesis 2013 Jan
PMID:Transcriptional networks that mediate signals from reproductive tissues to influence lifespan. 2294 91

Positive transcription elongation factor b (P-TEFb) is an RNA polymerase II kinase that phosphorylates Ser2 of the carboxyl-terminal domain and promotes the elongation phase of transcription. Despite the fact that P-TEFb has role in many cellular processes, the role of this kinase complex remains to be understood in early developmental events. In this study, using immunocytochemical analyses, we find that the P-TEFb components, Cyclin T1, CDK9, and its T-loop phosphorylated form, are localized to nuclear speckles, as well as in nucleoli in mouse germinal vesicle oocytes. Moreover, using fluorescence in situ hybridization, we show that in absence of CDK9 activity, nucleolar integration, as well as production of 28S rRNA is impaired in oocytes and embryos. We also present evidence indicating that P-TEFb kinase activity is essential for completion of mouse oocyte maturation and embryo development. Treatment with CDK9 inhibitor, flavopiridol resulted in metaphase I arrest in maturing oocytes. Inhibition of CDK9 kinase activity did not interfere with in vitro fertilization and pronuclear formation. However, when zygotes or 2-cell embryos were treated with flavopiridol only in their G2 phase of the cell cycle, development to the blastocyst stage was impaired. Inhibition of the CDK9 activity after embryonic genome activation resulted in failure to form normal blastocysts and aberrant phosphorylation of RNA polymerase II CTD. In all stages analyzed, treatment with flavopiridol abrogated global transcriptional activity. Collectively, our data suggest that P-TEFb kinase activity is crucial for oocyte maturation, embryo development, and regulation of global RNA transcription in mouse early development.
Genesis 2016 09
PMID:Inhibition of P-TEFb disrupts global transcription, oocyte maturation, and embryo development in the mouse. 2748 4