Eukaryotic translation initiation factor 4E-binding protein 1 (also known as 4E-BP1) is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
that in humans is encoded by the ''EIF4EBP1''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
inhibits cap-dependent translation by binding to translation initiation factor eIF4E. Phosphorylation of 4E-BP1 results in its release from eIF4E, thereby allows cap-dependent translation to continue thereby increasing the rate of protein synthesis.
Phosphorylation
Phosphorylated 4E-BP1 is thought to be a marker of upstream signaling (mTOR) activation. 4E-BP1 has seven phospho-sites, the three most important of which are the initiation site Thr 37/Thr 46, the second site Thr 70, and the final site Ser65. Moreover, phosphorylation of Ser 65 and Thr 70 alone was not sufficient to block the inhibition of mRNA translation by 4E-BP1, suggesting that multiple phosphorylation events must be combined to increase the rate of protein synthesis.
Function
This gene encodes one member of a family of translation repressor proteins. The protein directly interacts with eukaryotic translation initiation factor 4E (
eIF4E
Eukaryotic translation initiation factor 4E, also known as eIF4E, is a protein in humans encoded by the ''EIF4E'' gene. eIF4E plays a central role in translation initiation and is involved in regulating protein synthesis. Its activity influences ...
), which is a limiting component of the multisubunit complex that recruits 40S ribosomal subunits to the 5' end of mRNAs. Interaction of this protein with eIF4E inhibits complex assembly and represses translation. This protein is phosphorylated in response to various signals including UV irradiation and insulin signaling, resulting in its dissociation from eIF4E and activation of cap-dependent mRNA translation.
High level of phosphorylated 4E-BP1 has been widely reported in human cancers, and is associated with a worse outcome in several malignancies.
Interactions
EIF4EBP1 has been shown to
interact with:
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EIF4E
Eukaryotic translation initiation factor 4E, also known as eIF4E, is a protein in humans encoded by the ''EIF4E'' gene. eIF4E plays a central role in translation initiation and is involved in regulating protein synthesis. Its activity influences ...
,
*
KIAA1303
Regulatory-associated protein of mTOR also known as raptor or KIAA1303 is an Signal transducing adaptor protein, adapter protein that is encoded in humans by the ''RPTOR'' gene. Two messenger RNA, mRNAs from the gene have been identified that en ...
,
Mammalian target of rapamycin
The mammalian target of sirolimus, rapamycin (mTOR), also referred to as the mechanistic target of rapamycin, and sometimes called FK506-binding protein 12-rapamycin-associated protein 1 (FRAP1), is a kinase that in humans is encoded by the ''M ...
(mTOR).
References
Further reading
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