RanBP1 Governs Spindle Assembly by Defining Mitotic Ran-GTP Production

Abstract

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.

SGK1, the New Player in the Game of Resistance: Chemo-Radio Molecular Target and Strategy for Inhibition

“…Now, also in liver models, we obtained similar results by SI113-dependent SGK1 inactivation. From a more functional point of view, however, the SI113-dependent SGK1 inhibition is expected to alter the capacity of RANBP1 to finetune the mitotic checkpoint and nuclear stability [82][83][84][85][86]. In fact, in our experimental conditions, treatment with SI113 determined a profound G2/M-phase perturbation [71].…”

Reprint of “Nuclear transport factors: global regulation of mitosis”

“…Still other relevant players were found to regulate RanGTP production and modulation. These include the RanGEF RCC1, the RanGAP, its activating partner RanBP1, and RanBP2 ( Figure 2A) [18,19 ]. Interestingly, some proteins that are nuclear in interphase and SAFs in mitosis, such as lamin B and Rae1, are part of a mitotic spindle matrix, an entity that includes all proteins encompassed in the cytoplasmic region of the spindle [9,[20][21][22].…”

“…Localization of RCC1 on chromatin has been seen to increase during mitosis [61,62], an increase tightly regulated by RanBP1 [19 ]. RanBP1, already known to increase the activity of the RanGAP, has been shown to bind to RCC1 and modulate RCC1's enzymatic activity, thus controlling the spatial organization and amplitude of the mitotic spindle [19 ]. Other experiments using beads coated with purified RCC1 in Xenopus egg extracts demonstrate that RCC1 is one of the minimal chromosome components able to generate a spindle [63 ].…”

Differential turnover of Nup188 controls its levels at centrosomes and role in centriole duplication

“…For example, a fraction of the Nup107-160 complex is recruited to kinetochores after nuclear envelope and NPC breakdown during mitosis (Belgareh et al, 2001; Loïodice et al, 2004; Zuccolo et al, 2007), where it helps to recruit the γ-Tubulin ring complex (Mishra et al, 2010). This association might also recruit NTRs and components of the Ran GTPase system, which also play a central role in spindle assembly (Clarke and Zhang, 2008; Zhang et al, 2014). Other nups have also been shown to interact with the mitotic spindle (Cross and Powers, 2011) and spindle assembly checkpoint components (Iouk et al, 2002; Lussi et al, 2010; Markossian et al, 2015; Ródenas et al, 2012; Rodriguez-Bravo et al, 2014; Schweizer et al, 2013).…”