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P-TEFb- the final frontier.

Kohoutek J - Cell Div (2009)

Bottom Line: P-TEFb enables transition from abortive to productive transcription elongation by phosphorylating carboxyl-terminal domain (CTD) in RNAPII and negative transcription elongation factors.Over the years, we have learned a great deal about molecular composition of P-TEFb complexes, their assembly and their role in transcription of specific genes, but function of P-TEFb in other physiological processes was not apparent until just recently.In light of emerging discoveries connecting P-TEFb to regulation of cell cycle, development and several diseases, I would like to discuss these observations as well as future perspectives.

View Article: PubMed Central - HTML - PubMed

Affiliation: Veterinary Research Institute, Hudcova 70, 621 00 Brno, Czech Republic. Kohoutek@vri.cz.

ABSTRACT
Regulation of gene expression is essential to all aspects of physiological processes in single-cell as well as multicellular organisms. It gives ultimately cells the ability to efficiently respond to extra- and intracellular stimuli participating in cell cycle, growth, differentiation and survival. Regulation of gene expression is executed primarily at the level of transcription of specific mRNAs by RNA polymerase II (RNAPII), typically in several distinct phases. Among them, transcription elongation is positively regulated by the positive transcription elongation factor b (P-TEFb), consisting of CDK9 and cyclin T1, T2 or K. P-TEFb enables transition from abortive to productive transcription elongation by phosphorylating carboxyl-terminal domain (CTD) in RNAPII and negative transcription elongation factors. Over the years, we have learned a great deal about molecular composition of P-TEFb complexes, their assembly and their role in transcription of specific genes, but function of P-TEFb in other physiological processes was not apparent until just recently. In light of emerging discoveries connecting P-TEFb to regulation of cell cycle, development and several diseases, I would like to discuss these observations as well as future perspectives.

No MeSH data available.


Related in: MedlinePlus

Role of P-TEFb in a broad spectrum of biological processes. P-TEFb (blue pentagon) participates in many different biological processes, such as development (light orange oval), cancer (violet oval), cell cycle (yellow oval), cytokine response (pink oval) and others (green oval). Abbreviations in each oval represent particular transcription factors which have been found to employ P-TEFb in given biological phenomena (more information in the text). Importantly, dysregulation of P-TEFb-dependent transcription factors involved in development or cell cycle could also significantly contribute to malignant transformation of normal cells, as depicted by arrows in this figure.
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Figure 4: Role of P-TEFb in a broad spectrum of biological processes. P-TEFb (blue pentagon) participates in many different biological processes, such as development (light orange oval), cancer (violet oval), cell cycle (yellow oval), cytokine response (pink oval) and others (green oval). Abbreviations in each oval represent particular transcription factors which have been found to employ P-TEFb in given biological phenomena (more information in the text). Importantly, dysregulation of P-TEFb-dependent transcription factors involved in development or cell cycle could also significantly contribute to malignant transformation of normal cells, as depicted by arrows in this figure.

Mentions: It is becoming increasingly clear that P-TEFb participates in broad spectrum of biological processes (Figure 4). It is feasible to assume that the same transcription factors, different co-factors and signaling pathways co-operating with P-TEFb in cell cycle and development will be involved in pathophysiological effects of P-TEFb in various diseases, too. Therefore, the final task will be to identify what differences in these regulatory circuits are. What is the nature of these changes and if there is a way, to revert de-repressed P-TEFb activity back to normal "physiological state".


P-TEFb- the final frontier.

Kohoutek J - Cell Div (2009)

Role of P-TEFb in a broad spectrum of biological processes. P-TEFb (blue pentagon) participates in many different biological processes, such as development (light orange oval), cancer (violet oval), cell cycle (yellow oval), cytokine response (pink oval) and others (green oval). Abbreviations in each oval represent particular transcription factors which have been found to employ P-TEFb in given biological phenomena (more information in the text). Importantly, dysregulation of P-TEFb-dependent transcription factors involved in development or cell cycle could also significantly contribute to malignant transformation of normal cells, as depicted by arrows in this figure.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2748068&req=5

Figure 4: Role of P-TEFb in a broad spectrum of biological processes. P-TEFb (blue pentagon) participates in many different biological processes, such as development (light orange oval), cancer (violet oval), cell cycle (yellow oval), cytokine response (pink oval) and others (green oval). Abbreviations in each oval represent particular transcription factors which have been found to employ P-TEFb in given biological phenomena (more information in the text). Importantly, dysregulation of P-TEFb-dependent transcription factors involved in development or cell cycle could also significantly contribute to malignant transformation of normal cells, as depicted by arrows in this figure.
Mentions: It is becoming increasingly clear that P-TEFb participates in broad spectrum of biological processes (Figure 4). It is feasible to assume that the same transcription factors, different co-factors and signaling pathways co-operating with P-TEFb in cell cycle and development will be involved in pathophysiological effects of P-TEFb in various diseases, too. Therefore, the final task will be to identify what differences in these regulatory circuits are. What is the nature of these changes and if there is a way, to revert de-repressed P-TEFb activity back to normal "physiological state".

Bottom Line: P-TEFb enables transition from abortive to productive transcription elongation by phosphorylating carboxyl-terminal domain (CTD) in RNAPII and negative transcription elongation factors.Over the years, we have learned a great deal about molecular composition of P-TEFb complexes, their assembly and their role in transcription of specific genes, but function of P-TEFb in other physiological processes was not apparent until just recently.In light of emerging discoveries connecting P-TEFb to regulation of cell cycle, development and several diseases, I would like to discuss these observations as well as future perspectives.

View Article: PubMed Central - HTML - PubMed

Affiliation: Veterinary Research Institute, Hudcova 70, 621 00 Brno, Czech Republic. Kohoutek@vri.cz.

ABSTRACT
Regulation of gene expression is essential to all aspects of physiological processes in single-cell as well as multicellular organisms. It gives ultimately cells the ability to efficiently respond to extra- and intracellular stimuli participating in cell cycle, growth, differentiation and survival. Regulation of gene expression is executed primarily at the level of transcription of specific mRNAs by RNA polymerase II (RNAPII), typically in several distinct phases. Among them, transcription elongation is positively regulated by the positive transcription elongation factor b (P-TEFb), consisting of CDK9 and cyclin T1, T2 or K. P-TEFb enables transition from abortive to productive transcription elongation by phosphorylating carboxyl-terminal domain (CTD) in RNAPII and negative transcription elongation factors. Over the years, we have learned a great deal about molecular composition of P-TEFb complexes, their assembly and their role in transcription of specific genes, but function of P-TEFb in other physiological processes was not apparent until just recently. In light of emerging discoveries connecting P-TEFb to regulation of cell cycle, development and several diseases, I would like to discuss these observations as well as future perspectives.

No MeSH data available.


Related in: MedlinePlus