Translationally controlled tumor protein interacts with nucleophosmin during mitosis in ES cells.
Somatic cell nuclear transfers and the generation of induced pluripotent stem cells provide potential routes towards non-immunogenic cell replacement therapies. Translationally controlled tumor protein (Tpt1) was recently suggested to regulate cellular pluripotency. Here we explore functions of Tpt1 in mouse embryonic stem (ES) cells. We find that Tpt1 is present in the nucleus and cytoplasm of ES cells, and that specifically nuclear Tpt1 decreases upon cell differentiation. We also find that endogenous Tpt1 forms a complex with endogenous nucleophosmin/nucleoplasmin family member 1 (Npm1) in a cell cycle dependent manner. The Tpt1-Npm1 complex peaks sharply during mitosis and is independent of phosphorylation by Polo-like kinase. Differentiation by retinoic acid decreases Tpt1-Npm1 complex levels. Moreover, Tpt1 knock-down or over-expression reduces proliferation whereas Npm1 over-expression increases proliferation in ES cells. Cells depleted for both Tpt1 and Npm1 exhibit significantly reduced proliferation compared to cells depleted for Tpt1 alone, whereas cells over-expressing both Tpt1 and Npm1 show normal proliferation. Our findings reveal a role for the Tpt1-Npm1 complex in cell proliferation and identify the Tpt1-Npm1 complex as a potential biomarker for mitotic ES cells.
Johansson
Helena
H
Department of Medical Biochemistry and Cell Biology, Gothenburg University, Gothenburg, Sweden.
Vizlin-Hodzic
Dzeneta
D
Simonsson
Tomas
T
Simonsson
Stina
S
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008938:Mitosis; D009687:Nuclear Proteins / Q000378:metabolism*; D000090243:Nucleophosmin; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D000090324:Tumor Protein, Translationally-Controlled 1; D000097869:Polo-Like Kinase 1
D015415:Biomarkers; D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D000090243:Nucleophosmin; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D000090324:Tumor Protein, Translationally-Controlled 1; D000097869:Polo-Like Kinase 1; C000715570:Npm1 protein, mouse; C000715648:Tpt1 protein, mouse