RanGAP1*SUMO1 is phosphorylated at the onset of mitosis and remains associated with RanBP2 upon NPC disassembly

Swaminathan, Sowmya; Kiendl, Florian Josef Werner; Körner, Roman; Lupetti, Raffaella; Hengst, Ludger; Melchior, Frauke

doi:10.1083/jcb.200309126

Cited by 57 publications

(62 citation statements)

References 26 publications

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“…For example, RCC1 is a specific target of cyclin B1-Cdk1 during mitosis (24,43,45), and phosphorylated RCC1 plays a role in maintaining the balance between RanGTP and RanGDP. In addition to RCC1, RanGAP1 associated with RanBP2 is also phosphorylated by Cdks during mitotic progression (25). In addition, Ras/Akt signaling pathways modulate phosphorylation and function of RanBP3, which regulates the Ran gradient through control of RCC1 activity (32).…”

Section: Discussionmentioning

confidence: 99%

“…RanGAP1 is phosphorylated by mitotic kinase cyclin B1-Cdk1, and this modification is important for interaction with Ran (25). Based on the regu- 2, shPlk1).…”

Section: Ranbp1 Phosphorylation Regulates Mitotic Progressionmentioning

confidence: 99%

“…Conversely, during mitosis, RCC1 is phosphorylated by CDK1-cyclin B protein kinase, and its phosphorylation allows dynamic interaction with chromosomes (24). Similar to RCC1, phosphorylation of RanGAP1 is required at the onset of mitosis and remains associated with RanBP2 in the GTP-GDP state of the Ran cycle during progression through mitosis (25). Ran-binding protein-1 (RanBP1) is a cell cycle-dependent regulator of the Ran network in mammalian cells (26).…”

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confidence: 99%

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Phosphorylation of Ran-binding Protein-1 by Polo-like Kinase-1 Is Required for Interaction with Ran and Early Mitotic Progression

Hwang¹,

Ji²,

Jang

2011

Journal of Biological Chemistry

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Polo-like kinase-1 (Plk1) is essential for progression of mitosis and localizes to centrosomes, central spindles, midbody, and kinetochore. Ran, a small GTPase of the Ras superfamily, plays a role in microtubule dynamics and chromosome segregation during mitosis. Although Ran-binding protein-1 (RanBP1) has been reported as a regulator of RanGTPase for its mitotic functions, the action mechanism between Ran and RanBP1 during mitosis is still unknown. Here, we demonstrated in vitro and in vivo phosphorylation of RanBP1 by Plk1 as well as the importance of phosphorylation of RanBP1 in the interaction between Plk1 and Ran during early mitosis. Both phosphorylation-defective and N-terminal deletion mutant constructs of RanBP1 disrupted the interaction with Ran, and depletion of Plk1 also disrupted the formation of a complex between Ran and RanBP1. In addition, the results from both ectopic expression of phosphorylation-defective mutant construct and a functional complementation on RanBP1 deficiency with this mutant indicated that phosphorylation of RanBP1 by Plk1 might be crucial to microtubule nucleation and spindle assembly during mitosis.

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Section: Discussionmentioning

confidence: 99%

“…RanGAP1 is phosphorylated by mitotic kinase cyclin B1-Cdk1, and this modification is important for interaction with Ran (25). Based on the regu- 2, shPlk1).…”

Section: Ranbp1 Phosphorylation Regulates Mitotic Progressionmentioning

confidence: 99%

mentioning

confidence: 99%

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Phosphorylation of Ran-binding Protein-1 by Polo-like Kinase-1 Is Required for Interaction with Ran and Early Mitotic Progression

Hwang¹,

Ji²,

Jang

2011

Journal of Biological Chemistry

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Section: Rcc1 and Rangap Activities Are Not Inhibited By Sorbitol Stressmentioning

confidence: 99%

“…Under these conditions, the stress kinase p38 underwent a rightward shift reflective of its phosphorylation ( Figure 5C). Though RCC1 and RanGAP are known to undergo multisite phosphorylation (Li and Zheng, 2004;Swaminathan et al, 2004), sorbitol stress affects neither the biochemical activity nor the relative levels of RCC1 and RanGAP isoforms resolved by 2D gel electrophoresis. RCC1 binds to chromatin through an interaction with histones H2A and H2B, and this interaction is known to promote RCC1-mediated catalysis of nucleotide exchange on Ran (Nemergut et al, 2001;Li et al, 2003).…”

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confidence: 99%

Hyperosmotic Stress Signaling to the Nucleus Disrupts the Ran Gradient and the Production of RanGTP

Kelley

Paschal

2007

MBoC

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The RanGTP gradient depends on nucleocytoplasmic shuttling of Ran and its nucleotide exchange in the nucleus. Here we show that hyperosmotic stress signaling induced by sorbitol disrupts the Ran protein gradient and reduces the production of RanGTP. Ran gradient disruption is rapid and is followed by early (10 -20 min) and late (30 -60 min) phases of recovery. Results from SB203580 and siRNA experiments suggest the stress kinase p38 is important for Ran gradient recovery. NTF2 and Mog1, which are transport factors that regulate the nuclear localization of Ran, showed kinetics of delocalization and recovery similar to Ran. Microinjection of a nuclear localization signal reporter protein revealed that sorbitol stress decreases the rate of nuclear import. Sorbitol stress also slowed RCC1 mobility in the nucleus, which is predicted to reduce RCC1 dissociation from chromatin and RanGTP production. This was tested using a FRET biosensor that registers nuclear RanGTP levels, which were reduced in response to sorbitol stress. Although sorbitol alters nucleotide levels, we show that inverting the GTP/GDP ratio in cells is not sufficient to disrupt the Ran gradient. Thus, the Ran system is a target of hyperosmotic stress signaling, and cells use protein localization-based mechanisms as part of a rapid stress response. INTRODUCTIONCells subjected to UV radiation or oxidative, mechanical, or aniso-osmotic stress undergo both short-and long-term adaptation. Hyperosmotic stress induces rapid dehydration that drives an increase in intracellular salt concentration and a decrease in cell volume, placing physical strain on both the cytoskeleton and the plasma membrane (Lang et al., 1998). In response to these changes, cells rapidly initiate a stress signaling cascade and attempt to restore iso-osmolarity through transport of inorganic ions and initiate an accompanying reorganization of the actin cytoskeleton (Haussinger, 1996;Di Ciano et al., 2002). Short-term recovery of cell volume is facilitated by increasing intracellular concentrations of inorganic ions; however, elevated levels of intracellular salts can be detrimental to protein structure and function (Yancey et al., 1982;Russo et al., 2003). Long-term adaptation to hyperosmotic stress is achieved through signal transduction pathways that communicate with the metabolic and transcriptional machinery, resulting in the production or accumulation of organic osmolytes that increase intracellular osmolarity without adversely affecting protein structure or function (O'Neill, 1999).One of the most thoroughly studied stress kinases is the mitogen-activated protein kinase (MAPK) p38. p38 and its yeast homologue Hog1p are activated in response to a wide variety of adverse environmental conditions. These include osmotic, UV, and mechanical stress. Cytokines, such as interleukins and tumor necrosis factor ␣ are also known to activate p38 (Ono and Han, 2000). Hog1p and p38 are both phosphorylated on a threonine, glycine, tyrosine (TGY) motif within the kinase activation loop (Thr 180 an...

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Structural basis for SUMO‐E2 interaction revealed by a complex model using docking approach in combination with NMR data

et al. 2005

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The interaction between small ubiquitin-related modifier SUMO and its conjugating-enzyme Ubc9 (E2) is an essential step in SUMO conjugation cascade. However, an experimental structure of such a transient complex is still unavailable. Here, a structural model of SUMO-3-Ubc9 complex was obtained with HADDOCK, combining NMR chemical shift mapping information. Docking calculations were performed using SUMO-3 and Ubc9 structures as input. The resulting complex reveals that the complementary surface electrostatic potentials contribute dominantly to the specific interaction. At the interface, similar numbers of oppositely-charged conserved residues are identified on the respective binding partners. Hydrogen bonds are formed in the vicinity of the interface to stabilize the complex. Comparison of the structure of SUMO-3-Ubc9 complex generated by HADDOCK and the experimental structures in free form indicates that SUMO-3 and Ubc9 maintain their respective fold as a whole after docking. However, the N-terminal helix alpha1 and its subsequent L1 loop of Ubc9 experience sizeable changes upon complex formation. They cooperatively move towards the hydrophilic side of the beta-sheet of SUMO-3. Our observations are consistent with the data from previous Ubc9 mutational analysis and conformational flexibility studies. Together, we have proposed that the SUMO-3-Ubc9 interaction is strongly electrostatically driven and the N terminus of Ubc9 shifts to SUMO-3 to facilitate the interaction. The NMR-based structural model, which provides considerable insights into the molecular basis of the specific SUMO-E2 recognition and interaction, implicates the general interaction mode between SUMO-3 and Ubc9 homologues from yeast to humans.

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RanGAP1*SUMO1 is phosphorylated at the onset of mitosis and remains associated with RanBP2 upon NPC disassembly

Cited by 57 publications

References 26 publications

Phosphorylation of Ran-binding Protein-1 by Polo-like Kinase-1 Is Required for Interaction with Ran and Early Mitotic Progression

Phosphorylation of Ran-binding Protein-1 by Polo-like Kinase-1 Is Required for Interaction with Ran and Early Mitotic Progression

Hyperosmotic Stress Signaling to the Nucleus Disrupts the Ran Gradient and the Production of RanGTP

Structural basis for SUMO‐E2 interaction revealed by a complex model using docking approach in combination with NMR data

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