Regulatory mechanisms of the anti-apoptotic NAIP gene during cellular stress and malignancy

Apoptosis, or programmed cell death, is a critical physiological process that is turned on and off as appropriate to eliminate abnormal cells. When this switching process goes awry, it can lead to a variety of diseases including cancer. The genetic mechanisms that inhibit activation of the apoptosis protein (IAP) family include molecules that sequester key enzymes necessary for turning on and sustaining the process of programmed cell death. Neuronal apoptosis inhibitory protein (NAIP) is particularly interesting because expression of NAIP is reported to be highly elevated in various leukemias. In addition, NAIP is commonly deleted in the most severe cases of spinal muscular atrophy (SMA) and studies also have shown that a specific copy of this gene is required to suppress replication of the bacterial pathogen that causes Legionnaire’s disease. Researchers have also proposed that expression of NAIP in neurons of patients with Alzheimer’s disease can limit the high levels of cell death. Mark Romanish is studying the expression and regulation of NAIP to better understand its role and function in health and disease. Apoptosis is a highly regulated process receiving many activating and inhibiting signals, but the final outcome relies on which signals tip the scale. Therefore, the question of gene regulation becomes particularly important since those genes capable of rapid activation are more likely to influence the ultimate fate of a cell.