How does E2F regulate the cell cycle?
The E2F family of transcription factors plays a central role in regulating cellular proliferation by controlling the expression of both the genes required for cell cycle progression, particularly DNA synthesis, and the genes involved with apoptosis.
What do E2F transcription factors do?
E2F transcription factors regulate the expression of a number of genes important in cell proliferation, particularly those involved in progression through G1 and into the S-phase of the cell cycle.
Is E2F a regulatory transcription factor?
The E2F proteins form a family of transcription factors that regulate the transition from the G1 to the S phase in the cell cycle.
How E2F transcription factors are regulated by pRb during the cell cycle?
pRb inhibits cellular proliferation by altering the expression of genes that promote cellular division through an interaction with the E2F transcription factors. Of the six E2F members (E2F1–E2F6), pRb interacts preferentially with E2F1–E2F4, whereas p107 and p103 interact with E2F4 and E2F5.
Is E2F a proto oncogene or a tumor suppressor gene?
Conclusion. E2F is the principal target of the tumor suppressor pRB and defects in the RB pathway are observed in almost all cancers. Upon oncogenic changes, E2F activates ARF , an upstream activator of p53 and TAp73 , resulting in the induction of apoptosis.
How does Rb inhibit E2F?
Rb proteins are thought to inhibit expression of E2F-regulated genes in two ways (Dyson et al., 2002): by directly binding and blocking the activation domain of E2F proteins or by active repression through the recruitment of HDAC, SWI/SNF factors, Polycomb group proteins (Dahiya et al., 2001) or methyltransferase ( …
What genes does E2F control?
E2F targets genes that encode proteins involved in DNA replication (for example DNA polymerase, thymidine kinase, dihydrofolate reductase and cdc6), and chromosomal replication (replication origin-binding protein HsOrc1 and MCM5).
What does Rb protein do?
The Rb protein is a tumor suppressor, which plays a pivotal role in the negative control of the cell cycle and in tumor progression. It has been shown that Rb protein (pRb) is responsible for a major G1 checkpoint, blocking S-phase entry and cell growth.
How does pRb regulate cell cycle?
One function of pRb is to prevent excessive cell growth by inhibiting cell cycle progression until a cell is ready to divide. When the cell is ready to divide, pRb is phosphorylated, inactivating it, and the cell cycle is allowed to progress.
What is E2F transcribe?
The E2 factor (E2F) family of transcription factors are downstream effectors of the retinoblastoma (RB) protein pathway and are believed to play a pivotal role in cell division control. Since its discovery, E2F has been viewed as a positive regulator of genes required for DNA synthesis.
What genes does E2F activate?
Is E2F a cyclin?
E2F binding sites are found in both the cyclin E and cyclin D1 promoters, both promoters are activated by E2F gene products, and at least for cyclin E, the E2F sites contribute to cell cycle-dependent control.
How does Rb and E2F work together?
The RB/E2F pathway regulates apoptosis, and RB inhibition of apoptosis is an important mechanism of tumor suppression whereby cells deficient for RB function can be eliminated by apoptosis. One manner through which RB can inhibit apoptosis is through its binding to RNA processing factors.
Is E2F a tumor suppressor gene?
5. Pivotal roles of E2F in tumor suppression. E2F plays crucial roles not only in cell proliferation but also in tumor suppression. E2F1−/− mice are prone to tumor formation [5] and overexpression of E2F1 induces apoptosis, suggesting that E2F contributes to tumor suppression through the induction of apoptosis.
Is E2F a tumor suppressor or oncogene?
Although it can function as an oncogene, E2F-1 has also been postulated to be a tumor suppressor because it can induce apoptosis. Mice with a homozygous deletion of E2F-1 have a defect in thymocyte apoptosis, show increased cellular proliferation, and eventually develop numerous tumors [43,201].
What happens when E2F is mutated?
Mutation of E2f-1 suppresses apoptosis and inappropriate S phase entry and extends survival of Rb-deficient mouse embryos. Mol Cell.
Is E2F a tumor suppressor gene or oncogene?
What is the consequence of inactivation of the E2F complex?
In summary, the prevailing view has been that phenotypes associated with the inactivation of specific E2F family members result from the loss of E2F-mediated activation or repression of genes directly involved in DNA synthesis, mitotic progression and apoptosis.
What can we learn from the isolation of E2F transcription factors?
The isolation of E2F transcription factors provided the key to our current understanding of RB-1 function in the regulation of the cell cycle and in tumor suppression. It is becoming more and more evident that the regulatory circuits governing the cell cycle are very complex and highly interlinked.
Is E2F a transcriptional activator or a mediator?
Since E2F can act as a mediator of transcriptional repression as well as a transcriptional activator depending on tissue type, cell cycle position, and the spectrum of transcription factors of a given cell, much care must be taken to deliver agents that influence E2F activity only to cells where the expected mode of action is beneficial.
How does E2F affect gene activity?
The net effect of E2F on the transcriptional activity of a particular gene may be the result of as yet poorly understood protein–protein interactions of E2F with other components of the transcriptional machinery, as well as it may reflect the readout of the different ways of regulating E2F activity, itself.
Does PRB bind to e2f-1-mediated transactivation?
When the first member of the E2F family, E2F-1, was cloned as a pRB binding protein, a strong transactivation domain was discovered in its C-terminus which overlapped with the pRB binding site [4], [5]. It was demonstrated that pRB can suppress E2F-1-mediated transactivation by direct binding to the C-terminus of E2F-1 [111], [112].