Ubiquitin interactions of NZF zinc fingers

Alam, Steven L.; Sun, Ji; Payne, Marielle; Welch, Brett D.; Blake, B. Kelly; Davis, Darrell R.; Meyer, Hemmo; Emr, Scott D.; Sundquist, Wesley I.

doi:10.1038/sj.emboj.7600114

Cited by 226 publications

(246 citation statements)

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“…The Nup153 and Nup358 zinc finger domains share tandem repeats of zinc fingers with a X 4 WXCX 2 CX 3 NX 6 CX 2 CX 5 consensus, characteristic of a broader class of zinc fingers (Wang et al, 2003). Yet, many residues in the nucleoporin zinc fingers are not conserved (see Figure 1A), which is significant because a small number of amino acids within a zinc finger scaffold can dictate specific partnerships (Alam et al, 2004). Moreover, the linker regions between these zinc fingers, which comprise ϳ45% of what is referred to as the zinc finger domain, are even less well conserved than the zinc finger motifs themselves.…”

mentioning

confidence: 91%

Nuclear Envelope Breakdown Is Coordinated by Both Nup358/RanBP2 and Nup153, Two Nucleoporins with Zinc Finger Modules

Prunuske

Liu

Elgort

et al. 2006

MBoC

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When higher eukaryotic cells transition into mitosis, the nuclear envelope, nuclear pore complexes, and nuclear lamina are coordinately disassembled. The COPI coatomer complex, which plays a major role in membrane remodeling at the Golgi, has been implicated in the process of nuclear envelope breakdown and requires interactions at the nuclear pore complex for recruitment to this new site of action at mitosis. Nup153, a resident of the nuclear pore basket, was found to be involved in COPI recruitment, but the molecular nature of the interface between COPI and the nuclear pore has not been fully elucidated. To better understand what occurs at the nuclear pore at this juncture, we have probed the role of the nucleoporin Nup358/RanBP2. Nup358 contains a repetitive zinc finger domain with overall organization similar to a region within Nup153 that is critical to COPI association, yet inspection of these two zinc finger domains reveals features that also clearly distinguish them. Here, we found that the Nup358 zinc finger domain, but not a zinc finger domain from an unrelated protein, binds to COPI and dominantly inhibits progression of nuclear envelope breakdown in an assay that robustly recapitulates this process in vitro. Moreover, the Nup358 zinc finger domain interferes with COPI recruitment to the nuclear rim. Consistent with a role for this pore protein in coordinating nuclear envelope breakdown, Nup358-specific antibodies impair nuclear disassembly. Significantly, targeting either Nup153 or Nup358 for inhibition perturbs nuclear envelope breakdown, supporting a model in which these nucleoporins play nonredundant roles, perhaps contributing to COPI recruitment platforms on both the nuclear and cytoplasmic faces of the pore. We found that an individual zinc finger is the minimal interface for COPI association, although tandem zinc fingers are optimal. These results provide new information about the critical components of nuclear membrane remodeling and lay the foundation for a better understanding of how this process is regulated. INTRODUCTIONThe nuclear envelope creates a barrier that is critical to maintenance of the environment in the nucleus, specialized to support transcription and DNA replication. This double lipid membrane bilayer consists of an outer nuclear membrane, which is continuous with the endoplasmic reticulum (ER), and an inner nuclear membrane, which contains at least 78 different proteins, anchored via protein-protein interactions to the underlying nuclear lamina and chromatin . The nuclear envelope is perforated by nuclear pores, through which communication between the cytoplasm and nucleus occurs (Suntharalingam and Wente, 2003;Weis, 2003;Fahrenkrog et al., 2004;Pante, 2004). Despite the large size of the macromolecular nuclear pore complex (125 MDa in vertebrates), it is comprised of only ϳ30 different proteins, or nucleoporins (Nups), each present in multiple copies (Rout et al., 2000;Cronshaw et al., 2002). In metazoan cells, all these components-the lamina, nuclear pores, as well as the ...

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confidence: 91%

Nuclear Envelope Breakdown Is Coordinated by Both Nup358/RanBP2 and Nup153, Two Nucleoporins with Zinc Finger Modules

Prunuske

Liu

Elgort

et al. 2006

MBoC

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“…At the N-terminus of VPS25, two PPXY motifs, PPVY (amino acid 5-8) and PPXY (amino acid [11][12][13][14], are important for the interaction with VPS22 and VPS36. Whereas the first motif exists only in yeast, the second PPXY motif is highly conserved through the kingdoms (see Supplementary material Figure S2C) [51,52]. The most conserved domain, the VPS36 domain, is at the C-terminus.…”

Section: Escrt-iimentioning

confidence: 99%

“…This phosphoinositide and ubiquitin binding is mediated by the N-terminal GLUE domain [50]. Whereas the yeast VPS36 contains two additional N-terminal zinc fingers (NZF), neither of the animal nor the single Arabidopsis and rice homologs possess this NZF domain (see Supplementary material Figure S2C) [51,52]. The most conserved domain, the VPS36 domain, is at the C-terminus.…”

Section: Escrt-iimentioning

confidence: 99%

Exploring the ESCRTing machinery in eukaryotes

Winter

Hauser

2006

Trends in Plant Science

164

200

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The profile of protein sorting into multivesicular bodies (MVBs) has risen recently with the identification of three heteromeric complexes known as ESCRT-I,-II,-III (Endosomal Sorting Complex Required for Transport). Genetic analyses in yeast have identified up to 15 soluble class E VPS (vacuolar protein sorting) proteins that have been assigned to the ESCRT machinery and function in cargo recognition and sorting, complex assembly, vesicle formation and dissociation. Despite their functional importance in yeast and mammalian cells, little is known about their presence and function in other organisms including plants. We have made use of the fully sequenced genomes of Arabidopsis thaliana and Oryza sativa, Drosophila melanogaster and Caenorhabditis elegans to explore the identity, structural characteristics and phylogenetic relationships of proteins assigned to the ESCRT machinery.Multivesicular bodies (MVBs) are late endosomal organelles with up to several hundred interluminal vesicles that originate by invagination and budding of the limiting endosomal membrane (Figure 1) [1,2]. MVBs are also prevacuolar compartments involved in the retrograde endocytotic pathway where, upon fusion to vacuoles or lysosomes, the interluminal vesicles are released [3][4][5][6]. In yeast and mammals, MVBs are involved in sorting and degradation of transmembrane surface proteins as transporters (e.g. GAP1, STE6 and PDR5), receptors (e.g. EGFR, GHR, STE3 and STE2), in budding of viruses (e.g. HIV, MuLV and RSV) and in lipid partitioning [7,8]. However, MVBs are also central for sorting vacuolar proteins directly from the late Golgi to the anterograde and biosynthetic pathway ( Figure 1) [9]. Furthermore, MVBs operate in the exocytotic pathway and the secreted interluminal vesicles are known as exosomes (Figure 1) [10][11][12]. Thus, MVBs act as an intermediate station for cargo on the way to degradation, intracellular recycling and secretion ( Figure 1). Although MVBs have been described in plants, little is known about their biogenesis, cargos and function [2,4,[13][14][15][16]. These studies show that plant MVBs are prevacuolar compartments and are labeled by vacuolar sorting receptor (VSR) antibodies such as BP80 [5,17]. Plant MVBs are not only involved in the transport of proteins to lytic but also to protein-storage vacuoles. As plasmalemmasomes in tobacco, MVBs have been implicated in the internalization of arabinogalactanrich plasma membrane proteins that are sequestered within the vacuole [18] Upstream cargo recognition and sorting system of the ESCRT machineryThe entry of membrane proteins into the MVB pathway starts with the binding of monoubiquitinated cargos to the outer endosomal membrane and the recruitment of the ESCRT-I complex. This membrane association is mediated by ubiquitin-binding proteins that contain one or two UIMs or a GAT domain in combination with protein domains that had been implicated in binding to membranes such as the phosphatidylinositol-3 phosphate (PI3P) binding FYVE finger domain (Figure...

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“…To counteract interaction of the overexpressed ubiquitin with such motifs, a plasmid encoding ubiquitin with the L8A/I44A mutations was created in the context of the deletion mutant UbR (UbR L8A/I44A). The double mutation (L8A/I44A) and the single mutation (I44A) have both been demonstrated to efficiently inhibit interaction of ubiquitin with UIMs (Beal et al, 1996;Shih et al, 2002) as well as with other ubiquitin-binding domains (Kang et al, 2003;Alam et al, 2004;Shiba et al, 2004). All the ubiquitin constructs were Myc-tagged in order to facilitate detection of exogenously expressed protein.…”

Section: Monoubiquitin-binding Proteins Are Essential For Endocytosismentioning

confidence: 99%

Cbl-dependent Ubiquitination Is Required for Progression of EGF Receptors into Clathrin-coated Pits

Stang

Blystad

Kazazic

et al. 2004

MBoC

146

168

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Ligand binding causes the EGF receptor (EGFR) to become ubiquitinated by Cbl upon association with the adaptor protein Grb2. We have investigated the role of ubiquitin and Grb2 in ligand-induced endocytosis of the EGFR. Incubation of cells with EGF on ice caused translocation of Grb2 and Cbl from the cytosol to the rim of coated pits. Grb2 with point mutations in both SH3 domains inhibited recruitment of the EGFR to clathrin-coated pits, in a Ras-independent manner. On overexpression of the Cbl-binding protein Sprouty, ubiquitination of the EGFR was inhibited, the EGFR was recruited only to the rim of coated pits, and endocytosis of the EGFR was inhibited. Conjugation-defective ubiquitin similarly inhibited recruitment of EGF-EGFR to clathrin-coated pits. Even though this does not prove that cargo must be ubiquitinated, this indicates the importance of interaction of ubiquitinated protein(s) with proteins harboring ubiquitininteracting domains. We propose that Grb2 mediates transient anchoring of the EGFR to an Eps15-containing molecular complex at the rim of coated pits and that Cbl-induced ubiquitination of the EGFR allows relocation of EGFR from the rim to the center of clathrin-coated pits.

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Ubiquitin interactions of NZF zinc fingers

Cited by 226 publications

References 75 publications

Nuclear Envelope Breakdown Is Coordinated by Both Nup358/RanBP2 and Nup153, Two Nucleoporins with Zinc Finger Modules

Nuclear Envelope Breakdown Is Coordinated by Both Nup358/RanBP2 and Nup153, Two Nucleoporins with Zinc Finger Modules

Exploring the ESCRTing machinery in eukaryotes

Cbl-dependent Ubiquitination Is Required for Progression of EGF Receptors into Clathrin-coated Pits

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