Nuclear reformation after mitosis requires downregulation of the Ran GTPase effector RanBP1 in mammalian cells

Ciciarello, Marilena; Roscioli, Emanuele; Fiore, Barbara; Francesco, Laura Di; Sobrero, Fabrizia; Bernard, Delphine; Mangiacasale, Rosamaria; Harel, Amnon; Schininà, Maria Eugenia; Lavia, Patrizia

doi:10.1007/s00412-010-0286-5

Cited by 20 publications

(17 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Particularly, RCC1 accumulates on chromatin at anaphase onset in cycling XEE (Arnaoutov and Dasso, 2003), and we wondered whether RRR complex-dependent partitioning of RCC1 between the chromatin-bound and -unbound pools might play a role in this phenomenon. Earlier studies have demonstrated mitotic regulation of mammalian RanBP1 through degradation and phosphorylation (Ciciarello et al, 2010; Hwang et al, 2011). We did not find any evidence that RanBP1 was subject to degradation during multiple cell cycles within cycling XEE (Figure 4A, upper panel).…”

Section: Resultsmentioning

confidence: 99%

RanBP1 Governs Spindle Assembly by Defining Mitotic Ran-GTP Production

2014

View full text Add to dashboard Cite

SUMMARY Accurate control of the Ran GTPase cycle depends on the regulated activity of RCC1, Ran’s nucleotide exchange factor. RanBP1 has been characterized as a co-activator of the Ran GTPase activating protein, RanGAP1. RanBP1 can also form a stable complex with Ran and RCC1, although the dynamics and function of this complex remain poorly understood. Here we show that formation of the heterotrimeric RCC1/Ran/RanBP1 complex in M-phase Xenopus egg extracts controls both RCC1’s enzymatic activity and partitioning between the chromatin-bound and soluble pools of RCC1. This mechanism is critical for spatial control of Ran-GTP gradients that guide mitotic spindle assembly. Moreover, phosphorylation of RanBP1 drives changes in the dynamics of chromatin-bound RCC1 pools at the metaphase-anaphase transition. Our findings reveal an important mitotic role for RanBP1, controlling the spatial distribution and magnitude of mitotic Ran-GTP production and thereby ensuring accurate execution of Ran-dependent mitotic events.

show abstract

Section: Resultsmentioning

confidence: 99%

RanBP1 Governs Spindle Assembly by Defining Mitotic Ran-GTP Production

2014

View full text Add to dashboard Cite

show abstract

“…Fig. S5) and are hypersensitive to Impβ1 knockdown (see Section 3.1), and that Impβ1 is known to regulate multiple aspects of mitosis [20,27], we investigated whether the decreased viability in Impβ1 siRNA-treated cells may be associated with a block in cell cycle/mitotic progression and whether this relates to the induction of cell death. To this end, we performed propidium iodide staining of malignant MCF10CA1h cells treated twice with 10 nM Impβ1 siRNA followed by flow cytometry (Fig.…”

Section: Impβ1 Sirna Induces Death In Malignant Cellsmentioning

confidence: 99%

Hyper-dependence of breast cancer cell types on the nuclear transporter Importin β1

Kuusisto

Jans

2015

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

View full text Add to dashboard Cite

We previously reported that overexpression of members of the Importin (Imp) superfamily of nuclear transporters results in increased nuclear trafficking through conventional transport pathways in tumour cells. Here we show for the first time that the extent of overexpression of Impβ1 correlates with disease state in the MCF10 human breast tumour progression system. Excitingly, we find that targeting Impβ1 activity through siRNA is >30 times more efficient in decreasing the viability of malignant ductal carcinoma cells compared to isogenic non-transformed counterparts, and is highly potent and tumour selective at subnanomolar concentrations. Tumour cell selectivity of the siRNA effects was unique to Impβ1 and not other Imps, with flow cytometric analysis showing >60% increased cell death compared to controls concomitant with reduced nuclear import efficiency as indicated by confocal microscopic analysis. This hypersensitivity of malignant cell types to Impβ1 knockdown raises the exciting possibility of anti-cancer therapies targeted at Impβ1.

show abstract

“…Indeed, it controls Anillin localization and triggers asymmetric membrane elongation during anaphase, defining spindle positioning at the center of the dividing cell (Silverman-Gavrila et al, 2008 ; Kiyomitsu and Cheeseman, 2012 ). Finally, during cytokinesis the RanGTP pathway regulates the activity of the kinesin Kif14/Nabkin in actin bundling (Carleton et al, 2006 ; Samwer et al, 2013 ) and coordinates nuclear membrane and NPC reassembly (Harel et al, 2003 ; Walther et al, 2003 ; Ciciarello et al, 2010 ; Roscioli et al, 2010 ; Forbes et al, 2015 ; Figure 1D ).…”

Section: Understanding the Rangtp Pathway Through The Identification mentioning

confidence: 99%

The RanGTP Pathway: From Nucleo-Cytoplasmic Transport to Spindle Assembly and Beyond

Cavazza

Vernos

2016

Front. Cell Dev. Biol.

113

127

View full text Add to dashboard Cite

The small GTPase Ran regulates the interaction of transport receptors with a number of cellular cargo proteins. The high affinity binding of the GTP-bound form of Ran to import receptors promotes cargo release, whereas its binding to export receptors stabilizes their interaction with the cargo. This basic mechanism linked to the asymmetric distribution of the two nucleotide-bound forms of Ran between the nucleus and the cytoplasm generates a switch like mechanism controlling nucleo-cytoplasmic transport. Since 1999, we have known that after nuclear envelope breakdown (NEBD) Ran and the above transport receptors also provide a local control over the activity of factors driving spindle assembly and regulating other aspects of cell division. The identification and functional characterization of RanGTP mitotic targets is providing novel insights into mechanisms essential for cell division. Here we review our current knowledge on the RanGTP system and its regulation and we focus on the recent advances made through the characterization of its mitotic targets. We then briefly review the novel functions of the pathway that were recently described. Altogether, the RanGTP system has moonlighting functions exerting a spatial control over protein interactions that drive specific functions depending on the cellular context.

show abstract

Nuclear reformation after mitosis requires downregulation of the Ran GTPase effector RanBP1 in mammalian cells

Cited by 20 publications

References 67 publications

RanBP1 Governs Spindle Assembly by Defining Mitotic Ran-GTP Production

RanBP1 Governs Spindle Assembly by Defining Mitotic Ran-GTP Production

Hyper-dependence of breast cancer cell types on the nuclear transporter Importin β1

The RanGTP Pathway: From Nucleo-Cytoplasmic Transport to Spindle Assembly and Beyond

Contact Info

Product

Resources

About