High impact information on NUP1

• The central domain of NUP1 consists of a series of degenerate repeats similar to those found in the nucleoskeletal protein NSP1, a protein that cross-reacts with monoclonal antibodies against NUP1 [1].
• The NUP1 protein is essential for cell viability, and overexpression from the yeast GAL10 promoter prevents further cell growth [1].
• The NUP1 gene encodes an essential component of the yeast nuclear pore complex [1].
• The nucleoporins Nup60p, Nup2p, and Nup1p form part of the nuclear basket structure of the Saccharomyces cerevisiae nuclear pore complex (NPC) [2].
• Kap122p bound to nucleoporins, specifically, to the peptide repeat-containing fragments of Nup1p and Nup2p [3].

Biological context of NUP1

• However, truncations of the N-glycosylated, lumenal domain of Pom152p and pom152 mutants lacking N-linked glycosylation sites are viable in combination with nup1Delta, suppress nup1Delta temperature sensitivity, and partially suppress the nuclear protein import defects associated with the deletion of NUP1 [4].
• In this report, we describe a role for the FXFG nucleoporin Nup2p, and possibly the related Nup1p, in the Cse1p-mediated nuclear export pathway [5].
• In addition, nup1 mutant cells become multinucleate at all temperatures, a phenotype suggestive of a defect in nuclear migration [6].
• A high affinity binding site for a Kap95p import complex was mapped to the C terminus of Nup1p, and, surprisingly, deletion of all FG repeats in that region did not eliminate binding of the complex [7].

Anatomical context of NUP1

• Although the sequence similarity among these three nucleoporins suggests that they have a similar role in the nuclear pore complex, NUP2, in contrast to NSP1 and NUP1, is not required for growth [8].
• The distant sequence similarity between Srp1p and the beta-catenin/desmoplakin family, coupled with the altered structure of the nuclear envelope in nup1 mutants, suggests that Srp1p may function in attachment of the nuclear pore complex to an underlying nuclear skeleton [9].
• Our results suggest that Nup1p may be required to retain the structural integrity between the nuclear envelope and an underlying nuclear scaffold, and that this connection is required to allow reorientation of the nucleus in response to cytoskeletal forces [6].

Associations of NUP1 with chemical compounds

• We show that Nle3p coprecipitates with glutathione S-transferase fusions containing the amino-terminal domain of Nup1p [10].
• At each site, phenylalanine residues from Nup1p are buried in hydrophobic depressions between adjacent HEAT repeats [11].
• Indirect immunofluorescence experiments using antibody to N2,N2 dimethylguanosine-specific tRNA methyltransferase, a tRNA processing enzyme, and to Nup1p, a nuclear pore protein, show that both locate to the nuclear periphery in wild type cells [12].

Physical interactions of NUP1

• Genetic and physical interactions between Srp1p and nuclear pore complex proteins Nup1p and Nup2p [9].

Other interactions of NUP1

• Yeast cells lacking Nup2p or containing a particular temperature-sensitive mutation in NUP1 accumulate Srp1p in the nucleus [5].
• A nup1 deletion is lethal in combination with pom152Delta, as well as with truncations of the N-terminal and transmembrane regions of Pom152p [4].
• We have identified loss-of-function alleles of ALG12, encoding a mannosyltransferase, as suppressors of a temperature-sensitive mutation in the gene encoding the FXFG-nucleoporin NUP1 [4].
• Immunoelectron microscopy confirms that these densities contain XFXFG nucleoporins. act2-1 is synthetically lethal in combination with a deletion in the XFXFG nucleoporin gene, NUP1, or a mutation in the nuclear localization sequence receptor gene, SRP1 [13].
• In contrast, no accumulation of any pre-tRNA was observed in strains mutant for Nup1p, Nup85p, or Nup100p [14].

Analytical, diagnostic and therapeutic context of NUP1

• We have cloned a gene encoding one of these proteins (NUP1) and have confirmed the localization of the NUP1 protein to the pore complex by immunofluorescence, using an epitope-tagged construct to differentiate it from other members of this family [1].

References