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How 4E BP1 inhibits translation?

How 4E BP1 inhibits translation?

The 4E-BPs inhibit translation in a reversible manner. Hypophosphorylated 4E-BPs interact avidly with eIF4E, whereas 4E-BP hyperphosphorylation, elicited by stimulation of cells with hormones, cytokines, or growth factors, results in an abrogation of eIF4E-binding activity.

What does 4E BP1 do?

mTOR/4E-BP1 signaling pathway The mTOR pathway regulates major cellular processes and is implicated in several pathological conditions, including cancer, obesity, type 2 diabetes, and neurodegeneration. Typically, translation is regulated at the initiation phase, when a ribosome is recruited to the 5′-cap of an mRNA.

Is RHEB a GTPase?

Rheb has intrinsic GTPase activity and can alternate between an active GTP-bound form and an inactive GDP-bound form [14]. In yeasts (S. cerevisiae, S. pombe), Rheb is encoded by a single gene [13].

How do I activate mTOR signaling?

GTPases can activate mTORC2 indirectly via PI3K. Ras-GTP, but not Ras-GDP, interacts with PI3K and increases its activity [91]. Rab35, another small GTPase, was identified in an shRNA screen as a regulator of growth factor-stimulated PI3K signaling [92], which then activates mTORC2.

What does ULK1 stand for?

ULK1 (Unc-51 Like Autophagy Activating Kinase 1) is a Protein Coding gene. Diseases associated with ULK1 include Acute Laryngopharyngitis and Tuberous Sclerosis 1. Among its related pathways are Macroautophagy and Vesicle-mediated transport.

How is RHEB activated?

A model for the action of Rheb on mTORC1. Rheb in its GTP-bound state interacts with mTORC1 and activates it. This involves enhanced recruitment of substrate proteins resulting in their phosphorylation.

What does RHEB stand for?

RHEB also known as Ras homolog enriched in brain (RHEB) is a GTP-binding protein that is ubiquitously expressed in humans and other mammals. The protein is largely involved in the mTOR pathway and the regulation of the cell cycle.

What increases mTOR?

Both strength training and eating a meal rich in amino acids result in an increase in protein synthesis. The increase in protein synthesis in both cases is dependent on a protein kinase called the mammalian target of rapamycin (mTOR).

Which function is controlled by mTORC2?

Function. Though less understood than mTORC1, mTORC2 has been shown to respond to growth factors and to modulate cell metabolism and cell survival, thanks to its activation of the survival kinase Akt. mTORC2 activation by growth factors is done through promotion of mTORC2-ribosome association in PI3K-dependent manner.

How is hypophosphorylation of 4E-BP1 related to eIF4E binding?

Hypophosphorylated 4E-BP1 interacts strongly with eIF4E, whereas hyperphosphorylation of 4E-BP1 drastically decreases its binding to eIF4E.

How is 4E-BP1 phosphorylated in quiescent cells?

4E-BP1 is hypophosphorylated in quiescent cells, but is hyperphosphorylated on multiple sites following exposure to a variety of extracellular stimuli. The PI3-kinase/Akt pathway and the kinase FRAP/mTOR signal to 4E-BP1. FRAP/mTOR has been reported to phosphorylate 4E-BP1 directly in vitro.

Which is the gene for translation initiation factor 4E-BP1?

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.

Which is rapamycin sensitive component of the 4E-BP1 phosphorylation pathway?

The rapamycin-sensitive component in the 4E-BP1 phosphorylation pathway is FRAP/mTOR (FKBP12-rapamycin associated protein/mammalian target of rapamycin), also known as RAFT1 (rapamycin and 12-kD FK506 binding protein target 1), a member of the PIK (phosphoinositide kinase-related) family of kinases.