Serum-dependent and independent regulation of PARP2.

PARP2 belongs to a family of proteins involved in cell differentiation, DNA damage repair, cellular energy expenditure, chromatin modeling and cell differentiation. In addition to these overlapping functions with PARP1, PARP2 participates in spermatogenesis, T-cell maturation, extraembryonic endoderm formation, adipogenesis, lipid metabolism and cholesterol homeostasis. The function(s) of PARP2 is far from complete, and the mechanism(s) by which the gene and protein are regulated are unknown. In this study, we found that two different mechanisms are used in vitro to regulate PARP2 levels. In the presence of serum, PARP2 is degraded through the ubiquitin-proteasome pathway, however, when serum is removed or dialyzed with a 3.5 kDa molecular cut membrane, PARP2 rapidly becomes SDS and urea-insoluble. Despite the presence of a putative serum response element in the PARP2 gene, transcription is not affected by serum deprivation and PARP2 levels are restored when serum is replaced. The loss of PARP2 affects cell differentiation and gene expression linked to cholesterol and lipid metabolism. These observations highlight the critical roles PARP2 plays under different physiological conditions and reveal that PARP2 is tightly regulated by distinct pathways.