Cell cycle-dependent phosphorylation of nucleophosmin and its potential regulation by peptidyl-prolyl cis/trans isomerase.
Nucleophosmin (NPM) is a ubiquitously expressed phosphoprotein involved in many cellular processes. Phosphorylation is considered the major regulatory mechanism of the NPM protein, associated with diverse cellular events. In this study, we characterized the phosphorylation status of several physiological phosphorylation sites of NPM, especially the newly confirmedin vivosite threonine 95 (Thr95). NPM-Thr95 exhibits a transient and cell cycle-dependent phosphorylation state compared to several otherin vivophosphorylation sites examined, including Ser4, Thr199 and Thr234/Thr237. In addition, we characterized a functional interaction between NPM and the peptidyl-prolyl isomerase Pin1, which specifically bind to each other during mitosis. The demonstration of this binding represents a novel post-phosphorylation regulatory mechanism for NPM that has not been investigated before. Mutated Pin1 putative binding sites result in defected cell division and reduced number of mitotic cells, suggesting that post-phosphorylation is important for NPM in regulating cell cycle progression.
Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892.
Xuelian
X
Zhao
Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892.
Junfang
J
Ji
Laboratory of Proteomics and Analytical Technologies, SAIC-Frederick, Inc. Frederick National Laboratory for Cancer Research, Frederick, MD 20702.
Li-Rong
LR
Yu
Laboratory of Proteomics and Analytical Technologies, SAIC-Frederick, Inc. Frederick National Laboratory for Cancer Research, Frederick, MD 20702.
Timothy
T
Veenstra
Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892.
Xin Wei
XW
Wang