EIF2AK4 : eukaryotic translation initiation factor 2 alpha kinase 4

The EIF2AK4 Gene: Guardian of Cellular Health Under Stress

Hidden within our genetic code lies the EIF2AK4 gene, a master regulator of cellular response to stress. This gene encodes a protein called eukaryotic translation initiation factor 2-alpha kinase 4 (EIF2AK4), which acts as a vigilant sentinel, detecting and responding to various cellular stressors. But what happens when this gene malfunctions? The answer lies in understanding rare but serious lung conditions like pulmonary veno-occlusive disease (PVOD) and pulmonary hypertension (PH).

What is EIF2AK4?

EIF2AK4, also known as GCN2, is a protein kinase that plays a crucial role in the integrated stress response (ISR). The ISR is a complex cellular pathway activated when cells encounter stress, such as amino acid deprivation, viral infection, or protein misfolding. EIF2AK4 senses these stressors and triggers a cascade of events that help the cell adapt and survive.

EIF2AK4 and Lung Health

The EIF2AK4 gene is particularly important for lung health. Mutations in this gene have been strongly linked to the development of:

• Pulmonary Veno-Occlusive Disease (PVOD): A rare and life-threatening lung disorder characterized by blockage of small veins in the lungs, leading to high blood pressure and difficulty breathing.
• Pulmonary Hypertension (PH): A group of disorders characterized by high blood pressure in the arteries of the lungs, causing shortness of breath, fatigue, and other complications.

How Does EIF2AK4 Work?

EIF2AK4 functions as a molecular switch. When a cell encounters stress, EIF2AK4 becomes activated and phosphorylates a protein called eukaryotic translation initiation factor 2 alpha (eIF2α). This phosphorylation event leads to a reduction in protein synthesis, allowing the cell to conserve energy and resources until the stress is resolved.