E2F transcription factor
Introduction
The E2F transcription factor is a family of proteins that play a crucial role in controlling the cell cycle and the synthesis of DNA in mammals. This family of transcription factors is characterized by a specific DNA binding domain, which allows them to bind to specific sequences in the genome and regulate the transcription of target genes.
Structure
The E2F family of transcription factors consists of eight members, E2F1 through E2F8. These proteins share a highly conserved DNA binding domain, which enables them to bind to specific DNA sequences and regulate gene expression. The DNA binding domain of E2F proteins is composed of a series of alpha helices and beta sheets, which form a structure known as a helix-turn-helix motif. This motif is responsible for the specific interaction of E2F proteins with their target DNA sequences.
Function
E2F transcription factors are primarily known for their role in cell cycle regulation. They control the progression of the cell cycle by regulating the expression of genes required for DNA synthesis and cell division. In particular, E2F proteins are critical for the transition from the G1 phase to the S phase of the cell cycle, a process known as the G1/S transition.
E2F transcription factors also play a role in other cellular processes, including apoptosis, differentiation, and DNA damage response. For example, E2F1, one of the best-studied members of the E2F family, is known to induce apoptosis in response to DNA damage.
Regulation
The activity of E2F transcription factors is tightly regulated by a number of mechanisms. One of the main regulators of E2F activity is the Rb protein. In its hypophosphorylated state, Rb binds to E2F and inhibits its transcriptional activity. During the G1 phase of the cell cycle, Rb becomes phosphorylated and releases E2F, allowing it to activate the transcription of genes required for DNA synthesis and cell division.
Other proteins also regulate the activity of E2F transcription factors. For example, the DP family of proteins forms heterodimers with E2F proteins, which enhances their DNA binding activity. Additionally, the activity of E2F proteins can be regulated by post-translational modifications, such as phosphorylation and acetylation.
Role in Cancer
Given their critical role in cell cycle regulation, it is not surprising that E2F transcription factors are often implicated in cancer. Abnormal regulation of E2F activity can lead to uncontrolled cell proliferation, a hallmark of cancer. For example, mutations in the Rb gene that prevent it from inhibiting E2F activity are commonly found in a variety of cancers.
In addition to their role in cell proliferation, E2F transcription factors also contribute to the survival and resistance of cancer cells. For example, E2F1 has been shown to promote the survival of cancer cells by upregulating the expression of anti-apoptotic genes.