EIF4E

1. 본문

EIF4E (Eukaryotic translation initiation factor 4E) is a protein encoded by the *EIF4E* gene in humans. It plays a crucial role in the initiation of protein synthesis and has other functions related to RNA metabolism.

Here's a breakdown of EIF4E's key aspects:
Function:

• Translation Initiation: EIF4E is a vital component of the eIF4F complex, recognizing and binding to the 7-methylguanosine (m7G) cap structure found at the 5' end of most eukaryotic messenger RNAs (mRNAs). This binding is often the rate-limiting step in translation initiation. By binding the cap, eIF4E helps recruit ribosomes to the mRNA, initiating protein synthesis.
• mRNA Export: It participates in exporting a subset of mRNAs from the nucleus to the cytoplasm. This relies on its capability to bind to the m7G cap of RNAs.
• Regulation of Translation and Stability: Beyond initiation, eIF4E can influence the translation and stability of mRNA in the cytoplasm. It's a part of complexes that can repress translation or mediate the storage of inactive mRNAs.
• Spermatogenesis: It may contribute to spermatogenesis via translational regulation of specific mRNAs during germ cell development.

Structure:

• It's a 24-kD polypeptide.
• EIF4E exists both freely and as part of the eIF4F complex. The eIF4F complex includes eIF4E (the cap-binding protein), eIF4G (a scaffolding protein), and eIF4A (an RNA helicase).

Mechanism:1. EIF4E binds to the m7G cap of mRNA.

2. It recruits eIF4G and eIF4A, forming the eIF4F complex.

3. eIF4A, brought in by eIF4E, uses its helicase activity to unwind the secondary structure at the 5' end of the mRNA.

4. The eIF4F complex helps recruit the 43S pre-initiation complex (PIC), forming the 48S PIC.

5. Ribosome binding and translation initiation proceed.
Regulation:

• Inhibitory Proteins: EIF4E's activity is regulated by interactions with binding proteins, such as 4E-BPs (eIF4E-binding proteins).
• Phosphorylation: Phosphorylation of eIF4E at serine 209 can also regulate its activity.
• Transcriptional control: The amount of eIF4E protein can be regulated at the level of gene transcription.

Clinical Significance:

• Cancer: EIF4E acts as a proto-oncogene. Its overexpression and increased activity are linked to cell transformation and tumorigenesis. Because of this it is an important target for tumor therapy.
• Autism: EIF4E has also been associated with autism spectrum disorders.
• Psoriasis: EIF4E may play a role in psoriasis.
• Post-stroke Depression: Inhibition of eIF4e can cause post-stroke depression.

There are three members of the eIF4E family in mammals: eIF4E1 (eIF4E), eIF4E2, and eIF4E3. They have different structures, expression patterns and functions. eIF4E1 is present in all eukaryotes.