Dynamics and diverse functions of nuclear pore complex proteins

Chatel, Guillaume; Fahrenkrog, Birthe

doi:10.4161/nucl.19674

Cited by 37 publications

(32 citation statements)

References 104 publications

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“…Existing data support a role of APC as a linker between the nuclear envelope and microtubules, which might contribute to the role of APC in directed migration (Collin et al, 2008;Murawala et al, 2009). In addition, the emergence of nuclear pore proteins as regulators of mitosis, and the ability of APC to bind to microtubules and kinetochore proteins, raises the possibility that APC acts as a physical link between nuclear pore proteins and mitotic spindles (Chatel and Fahrenkrog, 2012;Dikovskaya et al, 2007;Kaplan et al, 2001).…”

Section: Regions Of Apc Involved In Proteinprotein Interactionsmentioning

confidence: 99%

Interactions and functions of the adenomatous polyposis coli (APC) protein at a glance

Nelson

Näthke

2013

Journal of Cell Science

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Section: Regions Of Apc Involved In Proteinprotein Interactionsmentioning

confidence: 99%

Interactions and functions of the adenomatous polyposis coli (APC) protein at a glance

Nelson

Näthke

2013

Journal of Cell Science

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“…The spatial distribution of individual nucleoporins within the NPC structure could vary [14]. Although the nucleoporins are fundamentally expected to be involved in the regulation of nucleo-cytoplasmic transport, several of them are shown to have multiple other functions [15,16].…”

Section: Introductionmentioning

confidence: 99%

Nup358 binds to AGO proteins through its SUMO ‐interacting motifs and promotes the association of target mRNA with miRISC

et al. 2016

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MicroRNA (miRNA)-guided mRNA repression, mediated by the miRNA-induced silencing complex (miRISC), is an important component of post-transcriptional gene silencing. However, how miRISC identifies the target mRNA in vivo is not well understood. Here, we show that the nucleoporin Nup358 plays an important role in this process. Nup358 localizes to the nuclear pore complex and to the cytoplasmic annulate lamellae (AL), and these structures dynamically associate with two mRNP granules: processing bodies (P bodies) and stress granules (SGs). Nup358 depletion disrupts P bodies and concomitantly impairs the miRNA pathway. Furthermore, Nup358 interacts with AGO and GW182 proteins and promotes the association of target mRNA with miRISC. A well-characterized SUMO-interacting motif (SIM) in Nup358 is sufficient for Nup358 to directly bind to AGO proteins. Moreover, AGO and PIWI proteins interact with SIMs derived from other SUMO-binding proteins. Our study indicates that Nup358-AGO interaction is important for miRNA-mediated gene silencing and identifies SIM as a new interacting motif for the AGO family of proteins. The findings also support a model wherein the coupling of miRISC with the target mRNA could occur at AL, specialized domains within the ER, and at the nuclear envelope.

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“…4 We recently reported an additional mechanism centered on the NUP98 moiety, thus potentially common to all NUP98 fusion oncoproteins, 18 which stems from the increasing appreciation that NUP98, like other nucleoporins, is implicated is several processes, in addition to nucleocytoplasmic transport, including mitotic progression see. 9 We demonstrated that NUP98 oncoproteins interfere with the function of the anaphase-promoting complex (APC/C), leading to an attenuation of the mitotic checkpoint (or spindle assembly checkpoint, SAC), ultimately resulting in whole chromosome instability. 18 Chromosomal instability due to deregulation of the mitotic checkpoint has been shown to increase the predisposition to malignant transformation, [25][26][27] and, more specifically, the misregulation of APC/C components has been reported to be associated with a number of human malignancies.…”

Section: Discussionmentioning

confidence: 99%

“…[5][6][7][8] NUP98, however, has been implicated, like other nucleoporins, in several additional processes, such as transcriptional regulation and mitotic progression. 2,9 The NUP98 protein contains 2 main functional domains: a GLFG repeat region, which serves as a nuclear transport receptor docking surface 7,10 ; and a GLEBS-like domain, which mediates the interaction with the RAE1 mRNA nuclear export factor. 11 Both domains are located within the N-terminal half of the NUP98 protein, spanning from amino acids 1 to »470, which is present in essentially all NUP98 fusion oncoproteins.…”

Section: Introductionmentioning

confidence: 99%

NUP98 fusion oncoproteins interact with the APC/C^Cdc20as a pseudosubstrate and prevent mitotic checkpoint complex binding

2016

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NUP98 is a recurrent partner gene in translocations causing acute myeloid leukemias and myelodisplastic syndrome. The expression of NUP98 fusion oncoproteins has been shown to induce mitotic spindle defects and chromosome missegregation, which correlate with the capability of NUP98 fusions to cause mitotic checkpoint attenuation. We show that NUP98 oncoproteins physically interact with the APC/C Cdc20 in the absence of the NUP98 partner protein RAE1, and prevent the binding of the mitotic checkpoint complex to the APC/C Cdc20 . NUP98 oncoproteins require the GLEBS-like domain present in their NUP98 moiety to bind the APC/C Cdc20 . We found that NUP98 wild-type is a substrate of APC/C Cdc20 prior to mitotic entry, and that its binding to APC/C Cdc20 is controlled via phosphorylation of a PEST sequence located within its C-terminal portion. We identify S606, within the PEST sequence, as a key target site, whose phosphorylation modulates the capability of NUP98 to interact with APC/C Cdc20 . We finally provide evidence for an involvement of the peptidyl-prolyl isomerase PIN1 in modulating the possible conformational changes within NUP98 that lead to its dissociation from the APC/C Cdc20 during mitosis. Our results provide novel insight into the mechanisms underlying the aberrant capability of NUP98 oncoproteins to interact with APC/C Cdc20 and to interfere with its function.

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Dynamics and diverse functions of nuclear pore complex proteins

Cited by 37 publications

References 104 publications

Interactions and functions of the adenomatous polyposis coli (APC) protein at a glance

Interactions and functions of the adenomatous polyposis coli (APC) protein at a glance

Nup358 binds to AGO proteins through its SUMO ‐interacting motifs and promotes the association of target mRNA with miRISC

NUP98 fusion oncoproteins interact with the APC/C^Cdc20as a pseudosubstrate and prevent mitotic checkpoint complex binding

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Dynamics and diverse functions of nuclear pore complex proteins

Cited by 37 publications

References 104 publications

Interactions and functions of the adenomatous polyposis coli (APC) protein at a glance

Interactions and functions of the adenomatous polyposis coli (APC) protein at a glance

Nup358 binds to AGO proteins through its SUMO ‐interacting motifs and promotes the association of target mRNA with miRISC

NUP98 fusion oncoproteins interact with the APC/CCdc20as a pseudosubstrate and prevent mitotic checkpoint complex binding

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NUP98 fusion oncoproteins interact with the APC/C^Cdc20as a pseudosubstrate and prevent mitotic checkpoint complex binding