The role and regulation of Pnn in proliferative and non-dividing cells: Form embryogenesis to pathogenesis

Pnn, a multiple functional protein, plays roles in embryonic development, cellular differentiation, tumorigenesis, and metastasis. In the past two decades, the functions of Pnn in regulating RNA alternative splicing, gene regulation, and cell-cell connection have been revealed. Although Pnn is originally identified as a desmosome-associated protein for linking desmosome and intermediated filament, emerging evidence implies that Pnn not only is a desmosome protein but also plays critical roles in the nucleus. To date, through cell biology investigation and the generation of animal models with genetic manipulation, the physiological role of Pnn has been characterized in the research fields of developmental biology, tumor biology, and neuroscience. Through proteomic and molecular biology studies, transcription regulators, splicing regulators, and cytoskeletal proteins were found to interact with Pnn. In addition, histopathological and biochemical evidence has pointed to an association of Pnn expression level with tumorigenesis and metastasis. A previous clinical study also demonstrated a correlation between a reduced expression of Pnn and human dementia. Besides, experimental studies showed a protective role of Pnn against ischemic stress in astrocytes. All indicated a variety of roles of Pnn in different cell types. In this review article, we introduced the role of Pnn in embryogenesis and pathogenesis as well as discussed its potential clinical application.