EIF4G2

EIF4G2 encodes the eukaryotic translation initiation factor 4G2, a 97-kilodalton scaffold protein in the translation initiation machinery. It is a member of the eIF4G family and is also known as DAP5 (death-associated protein 5) or p97. Unlike the canonical eIF4G1, EIF4G2 lacks the traditional eIF4E-binding site, reflecting a specialized role in cap-independent translation.

Functionally, EIF4G2 acts as a scaffold that facilitates initiation of translation under conditions where cap-dependent initiation is downregulated, such as cellular stress. It participates in internal ribosome entry site (IRES)-mediated translation by forming complexes with initiation factors like eIF4A and eIF3 and binding to RNA elements. Through these interactions, EIF4G2 supports translation of a subset of mRNAs, including those encoding apoptosis regulators and proteins involved in cell survival and growth, helping cells cope with stress or maintain translation when general protein synthesis is suppressed.

Structurally, EIF4G2 contains MIF4G and MA3-type domains typical of the eIF4G family, enabling interaction with RNA and other initiation factors, while lacking the eIF4E-binding motif that couples to cap-dependent translation.

Clinical relevance and regulation: EIF4G2 is broadly expressed and its activity is linked to cellular stress responses, hypoxia, and viral infection. Dysregulation of EIF4G2-dependent, cap-independent translation has been observed in some cancers and may influence tumor progression by promoting the synthesis of specific survival-promoting proteins.