High impact information on NUP2

• Genetic studies, immunolocalization, live imaging, and chromatin immunoprecipitation experiments show that these transport proteins block spreading of heterochromatin by physical tethering of the HML locus to the Nup2p receptor of the nuclear pore complex [1].
• The mobile nucleoporin Nup2p and chromatin-bound Prp20p function in endogenous NPC-mediated transcriptional control [2].
• Among these, Nup2p is unique as it transiently associates with NPCs and, when artificially tethered to DNA, can prevent the spread of transcriptional activation or repression between flanking genes, a function termed boundary activity [2].
• Nup2p binds Kap60p more strongly than NLSs and accelerates release of NLSs from Kap60p [3].
• Structural basis for Nup2p function in cargo release and karyopherin recycling in nuclear import [3].

Biological context of NUP2

• Nup2p is located at the nuclear side of the central gated channel of the NPC and provides a binding site for Srp1p via its amino-terminal domain [4].
• The yeast nucleoporin Nup2p is involved in nuclear export of importin alpha/Srp1p [5].
• In contrast, Nup2p uses a conserved sequence motif (VMXXRKIA) coupled to an AIS-like motif to accelerate dissociation of Kap60p.NLS complexes in a vectorial reaction mechanism [6].
• These results implicate the NBs in the maintenance of genomic stability and suggest that p95 and MRE11 may have roles in telomere maintenance in mammals, analogous to the role their homologues play in yeast [7].
• They also suggest that p95 has roles in regulating cell adhesion and morphology [8].

Anatomical context of NUP2

• Nup2p is located on the nuclear side of the nuclear pore complex and coordinates Srp1p/importin-alpha export [9].
• Like NUP1 and NSP1, NUP2 localizes to discrete spots in the nuclear envelope, as determined by indirect immunofluorescence [10].
• Yrb1p is located in the cytosol whereas Nup2p is nuclear [11].
• Immunoprecipitation from subcellular fractions yields only p110 and p95 from purified nuclei, whereas the approximately 55-kD protein is immunoprecipitated from the soluble fraction [12].
• In this study, we examined the effects of p95 on the anchorage-independent growth and tumorigenicity of malignant HeLa cells, and on the growth and morphology of non-transformed NIH3T3 cells [8].

Associations of NUP2 with chemical compounds

• Nup2p possesses a very large Stokes radius (79 A) in gel filtration columns, sediments slowly in sucrose gradients as a 2.9 S particle, and is highly sensitive to proteolytic digestion by proteinase K; these characteristics suggest a structure of low compactness and high flexibility [13].

Physical interactions of NUP2

• RanGTP export complex releases Srp1p from its binding site in Nup2p [5].
• On the nucleoplasmic face, where the Ran--GTP levels are predicted to be high, Nup2p binds to Nup60p [14].
• In a two-hybrid screen, we identified Nup2p as a nucleoporin interacting with Los1p [15].
• Unexpectedly, the same Nups also captured the hexameric Nup84p complex and Nup2p [16].

Other interactions of NUP2

• Yeast cells lacking Nup2p or containing a particular temperature-sensitive mutation in NUP1 accumulate Srp1p in the nucleus [9].
• We do not observe any biochemical interaction between Cse1p and Nup2p [9].
• A deletion of NUP2 shows genetic interactions with mutants in SRP1 and PRP20, which encodes the Ran nucleotide exchange factor [5].
• YRB2 encodes a protein containing a Ran-binding motif similar to that found in Yrb1p and Nup2p [11].
• 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 [10].

Analytical, diagnostic and therapeutic context of NUP2

• Examination of subcellular fractions by immunoblotting shows that both p110 and p95 are located exclusively in the nuclear fraction [12].
• Spectral analyses (CD and FTIR spectroscopy) provide additional evidence that Nup2p contains extensive regions of structural disorder with comparatively small contributions of ordered secondary structure [13].

References