Phosphorylation of nucleoporin Tpr governs its differential localization and is required for its mitotic function
| Autor: | Sagar Sengupta, Raina Priyadarshini, Vinay Kumar Nandicoori, Gagan Deep Jhingan, Anshuk Sarkar, Manisha Jalan, Kalpana Rajanala |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
inorganic chemicals
Mad1 Amino Acid Motifs Mitosis Biology environment and public health Proto-Oncogene Proteins Humans Protein phosphorylation Nuclear pore Phosphorylation Protein kinase A Cyclin-dependent kinase 1 Cell Biology Cyclic AMP-Dependent Protein Kinases Chromatin Cell biology Nuclear Pore Complex Proteins enzymes and coenzymes (carbohydrates) Protein Transport Mad2 Proteins Nuclear Pore Nucleoporin Research Article HeLa Cells Protein Binding |
| Zdroj: | Journal of cell science. 127(Pt 16) |
| ISSN: | 1477-9137 |
| Popis: | A major constituent of the nuclear basket region of the nuclear pore complex (NPC), nucleoporin Tpr, plays roles in regulating multiple important processes. We have previously established that Tpr is phosphorylated in both a MAP-kinase-dependent and MAP-kinase-independent manner, and that Tpr acts as both a substrate and as a scaffold for ERK2 (also known as MAPK1). Here, we report the identification of S2059 and S2094 as the major novel ERK-independent phosphorylation sites and T1677, S2020, S2023 and S2034 as additional ERK-independent phosphorylation sites found in the Tpr protein in vivo. Our results suggest that protein kinase A phosphorylates the S2094 residue and that the site is hyperphosphorylated during mitosis. Furthermore, we find that Tpr is phosphorylated at the S2059 residue by CDK1 and the phosphorylated form distinctly localizes with chromatin during telophase. Abrogation of S2059 phosphorylation abolishes the interaction of Tpr with Mad1, thus compromising the localization of both Mad1 and Mad2 proteins, resulting in cell cycle defects. The identification of novel phosphorylation sites on Tpr and the observations presented in this study allow better understanding of Tpr functions. |
| Databáze: | OpenAIRE |
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