DAP5 (Death Associated Protein 5), also named p97 and NAT1, is a member of the eIF4G family that lacks the eIF4E binding site. Its function was linked to programmed cell death (PCD) based on the seminal finding that a fragment of DAP5/p97 protein, which acted in a dominant-negative manner, protected against IFN-gamma (IFN-γ)-induced cell death. Subsequently, it was found that DAP5 protein is activated during cell death by caspase cleavage, yielding a C-terminal-truncated protein of 86 kDa. The p86 form promotes internal ribosome entry site (IRES)-dependent translation of several mRNAs including Apaf-1, c-myc, XIAP, HIAP2 and DAP5 itself, which carries an IRES element in its 5′UTR. The activation of DAP5 IRES creates a positive feedback loop, which results in sustained translation of DAP5 protein during PCD under conditions of reduced cap-dependent translation. DAP5 deficiency prevents embryonic stem (ES) cell differentiation, suggesting a wider range of DAP5 mRNA targets and additional mechanisms that might activate the protein.

Developmental processes and tissue homeostasis within a multicellular organism require a tight control over cell population size. This is achieved by a complicated set of genetically controlled and highly conserved processes, which lead to the death of a cell (named PCD). In general, the balance between cell death and survival signals, integrated via diverse cellular signaling pathways, dictates whether the individual cell will live or die.1

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