Disease relevance of NUP153

• Analysis of components of the NPC revealed that two proteins, Nup153 and p62, were proteolyzed during poliovirus infection [1].

High impact information on NUP153

• This giant protein comprises an amino-terminal 700-residue leucine-rich region, four RanBP1-homologous (refs 9, 10) domains, eight zinc-finger motifs similar to those of NUP153 (refs 11, 12), and a carboxy terminus with high homology to cyclophilin [2].
• We uncovered direct interactions of Smad2 with the nucleoporins CAN/Nup214 and Nup153 [3].
• Strikingly, Nup98 and Nup153 each bound the same four large proteins [4].
• Importin alpha/beta-mediated protein import into the nucleus was strongly reduced in the absence of Nup153, while transportin-mediated import was unaffected [5].
• The nucleoporin Nup153 is required for nuclear pore basket formation, nuclear pore complex anchoring and import of a subset of nuclear proteins [5].

Biological context of NUP153

• RanGTP-mediated nuclear export of karyopherin alpha involves its interaction with the nucleoporin Nup153 [6].
• The specificity of this interaction is demonstrated by its sensitivity to Tpr amino acid substitution mutations that abolish Tpr's ability to adhere to the NPC and affect the direct binding of Tpr to Nup153 [7].
• Substrate binding by the importin alpha.beta complex and the association of the complex with the nucleoporins Nup358/RanBP2 and Nup153 are not affected by phosphatase inhibitors, suggesting that transport inhibition by protein phosphorylation does not involve these steps [8].
• Four nucleoporins, Nup153, RanBP2, Nup214 and Tpr are cleaved by caspases during apoptosis [9].
• Nup153 contains separate binding sites for importin alpha/beta, which mediates classical NLS import, and for transportin, which mediates import of different nuclear proteins [10].

Anatomical context of NUP153

• A monoclonal antibody, termed QE5, recognized three NPC polypeptides, p250, NUP153, and p62 on Western blots, and labeled the nuclear envelope of several cultured cell lines by immunofluorescence microscopy [11].
• Labeling with these two antibodies has documented that NUP153 is a constituent of the nuclear basket with at least one of its epitopes residing in its terminal ring, whereas p250 is a constituent of the cytoplasmic filaments [11].
• By contrast, a group of nucleoplasmically oriented nucleoporins, including NUP153, NUP50, NUP96, and NUP93, had no affinity for annulate lamellae and assembled normally into nuclear pores [12].
• Nup153 is a peripheral NPC component that has been implicated in protein and RNP transport and in the interaction of NPCs with the nuclear lamina [5].
• In this study, anti-Nup153 antibodies were used to probe the role of Nup153 in nuclear export in Xenopus oocytes [13].

Associations of NUP153 with chemical compounds

• In contrast, ATP depletion, calcium store depletion by EGTA or thapsigargin, and high concentrations of divalent cation (i.e. 2 mM Ca(2+) and 2 mM Mg(2+)) constrain the distribution of the FG-repeats of Nup153 and Nup214 [14].
• Targeting information for Nup153 resides in the NH2-terminal domain since this region of the molecule can direct an ordinarily cytoplasmic protein, pyruvate kinase, to the nuclear face of the nuclear pore complex [15].
• Nup153 is a large O-linked glycoprotein that is a component of the basket-like structure that forms the nucleoplasmic face of nuclear pore complexes (NPCs) [16].

Physical interactions of NUP153

• Neither Nup153 fragment affected binding of the export receptor Crm1 at the nuclear rim [10].
• We show that Nup96 and Nup107 are core elements of the NPC proper that are essential for NPC assembly and docking of Nup153 and Tpr to the NPC [17].

Regulatory relationships of NUP153

• Carrier-independent nuclear import of the transcription factor PU.1 via RanGTP-stimulated binding to Nup153 [18].

Other interactions of NUP153

• Interestingly, FG repeat-containing segments derived from the nucleoporins NUP153 and CAN/NUP214 functioned similarly to those from NUP98 [19].
• The Ets domain accounted for the bulk of the interaction of PU.1 with Nup153 and RanGMPPNP [18].
• When lamina assembly is prevented using the dominant-negative mutant XlaminB delta 2+, Nup153 does not appear at the nuclear envelope, while other F/GXFG-containing nucleoporins and Nup93 are recruited normally [20].
• Nup93 and Nup205 are other NPC core elements that are important for long-term maintenance of NPCs but initially dispensable for the anchoring of Nup153 and Tpr [17].
• As LB, LAP2 and Nup153 are exposed at the inner face of the nuclear envelope and all interact with chromatin, we suggest that their cleavage allows both the detachment of NE from chromatin and the clustering of NPCs in the plane of the membrane, two conserved morphological features of apoptosis observed in this study [21].

Analytical, diagnostic and therapeutic context of NUP153

• By immunoprecipitation, we find the nucleoporin Nup153 and the pore-associated filament protein Tpr, previously shown to reside at distinct sites on the intranuclear side of assembled pores, are each in stable subcomplexes with importin alpha and beta in Xenopus egg extracts [22].
• In a search for proteins that moor Tpr to the NPC, we have combined the RNAi approach with affinity-chromatography and yeast two-hybrid interaction studies, leading to the identification of nucleoporin Nup153 as the binding partner for Tpr [7].
• Here, Nup153 is localized by immunogold electron microscopy to a position on the nuclear ring of the NPC [5].
• Sequence analysis of a cDNA encoding a human nuclear pore complex protein, hnup153 [23].

References