Nucleolin (NCL) is an abundant stress-responsive, RNA-binding phosphoprotein 
that controls gene expression by regulating either mRNA stability and/or 
translation. NCL binds to the AU-rich element (ARE) in the 3'UTR of target 
mRNAs, mediates miRNA functions in the nearby target sequences, and regulates 
mRNA deadenylation. However, the mechanism by which NCL phosphorylation affects 
these functions and the identity of the deadenylase involved, remain largely 
unexplored. Earlier we demonstrated that NCL phosphorylation is vital for cell 
cycle progression and proliferation, whereas phosphorylation-deficient NCL at 
six consensus CK2 sites confers dominant-negative effect on proliferation by 
increasing p53 expression, possibly mimicking cellular DNA damage conditions. In 
this study, we show that NCL phosphorylation at those CK2 consensus sites in the 
N-terminus is necessary to induce deadenylation upon oncogenic stimuli and UV 
stress. NCL-WT, but not hypophosphorylated NCL-6/S*A, activates poly 
(A)-specific ribonuclease (PARN) deadenylase activity. We further demonstrate 
that NCL interacts directly with PARN, and under non-stress conditions also 
forms (a) complex (es) with factors that regulate deadenylation, such as p53 and 
the ARE-binding protein HuR. Upon UV stress, the interaction of 
hypophosphorylated NCL-6/S*A with these proteins is favored. As an RNA-binding 
protein, NCL interacts with PARN deadenylase substrates such as TP53 and BCL2 
mRNAs, playing a role in their downregulation under non-stress conditions. For 
the first time, we show that NCL phosphorylation offers specificity to its 
protein-protein, protein-RNA interactions, resulting in the PARN deadenylase 
regulation, and hence gene expression, during cellular stress responses.