How does 4E BP1 inhibit translation?

How does 4E BP1 inhibit translation?

The eIF4E-binding proteins (4E-BPs) are a family of three small peptides that inhibit cap-dependent translation by binding to eIF4E and obstructing its interaction with eIF4G (Lin et al.

What is the function of eIF4G?

The eukaryotic initiation factor eIF4G is a large modular protein which serves as a docking site for initiation factors and proteins involved in RNA translation. Together with eIF4E and eIF4A, eIF4G constitutes the eIF4F complex which is a key component in promoting ribosome binding to the mRNA.

Does Mtor inhibit 4EBP1?

INK128, an MTOR Inhibitor, Inhibits HH Signaling in the Brain The unexpected critical role of MTOR-dependent translation in HH signaling and the high p-4EBP1 levels in SHH-group medul- loblastoma in humans prompted us to investigate the potential of MTOR inhibitors in treating SHH-group medulloblastoma.

What does 4EBP1 stand for?

Eukaryotic translation initiation factor 4E-binding protein 1 (also known as 4E-BP1) is a protein that in humans is encoded by the EIF4EBP1 gene.

How does 4E BP regulate the availability of active eIF4F?

2.2. The protein family 4E-BP regulates eIF4E capacity to form the cap-binding complex (eIF4F). In contrast, hypoxia induces a phosphorylation decrease in 4E-BP1 (Shenberger et al., 2005). When 4E-BPs are hypophosphorylated, they can sequestrate eIF4E and prevent the interaction with eIF4G and inhibit the translation.

What does the mTOR pathway do?

The mTOR signaling pathway, which is often activated in tumors, not only regulates gene transcription and protein synthesis to regulate cell proliferation and immune cell differentiation but also plays an important role in tumor metabolism.

Why is eIF4G important?

eIF4G acts as a major hub in initiation and mediates recruitment of additional initiation factors, providing a scaffold for ribosome/mRNA-bridging (Sonenberg et al., 1978). eIF4G also helps recruit the mRNA helicase eIF4A. Together, these three factors make up eIF4F, also known as the cap-binding complex.

What phosphorylates eIF4E?

eIF4E is phosphorylated by the MNK1/2 serine/threonine kinases, which are activated in response to mitogenic and stress signaling downstream of ERK1/2 and p38 MAP kinase, respectively (9, 10). eIF4E phosphorylation at serine 209 by MNK1/2 promotes its transformation activity (11, 12).

What phosphorylates 4ebp1?

Phosphorylated 4E-BP1 has been generally accepted as a marker of activated mTOR signaling. Seven phosphorylation sites have been identified in 4E-BP1: Thr 37, Thr 46, Ser 65, Thr 70, Ser 83, Ser 101, and Ser 112 (numbering based on human 4E-BP1; in rodents, the numbers are lower by one).

What is the function of eEF2?

Molecular Mechanisms of Memory Eukaryotic elongation factor 2 (eEF2) is a GTP-binding protein that mediates the translocation of peptidyl-tRNA from the A site to the P site on the ribosome (Moldave, 1985).

Is mTOR a kinase?

mTOR is a member of the phosphatidylinositol 3-kinase-related kinase family of protein kinases. As a core component of mTORC2, mTOR also functions as a tyrosine protein kinase that promotes the activation of insulin receptors and insulin-like growth factor 1 receptors.

Is mTOR activated by phosphorylation?

Phosphorylation of mammalian target of rapamycin (mTOR) at Ser-2448 is mediated by p70S6 kinase.