Characterization and Targeted Disruption of Murine Nup50, a p27<sup>Kip1</sup>-Interacting Component of the Nuclear Pore Complex

Smitherman, Matthew; Lee, Keesook; Swanger, Jherek; Kapur, Raj P.; Clurman, Bruce E.

doi:10.1128/mcb.20.15.5631-5642.2000

Cited by 105 publications

(111 citation statements)

References 33 publications

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“…NUP50 encodes for a nucleoporin complex component involved in nucleocytoplasmic protein trafficking. 8,9 Thus, in order to verify the microarray data by an alternative approach, 6 tumor specimens were randomly selected from each group of samples and the expression levels of GnT-IV and Nup50 were compared to the housekeeping gene, b-actin, by reverse transcription followed by PCR (Fig. 2).…”

Section: Resultsmentioning

confidence: 99%

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Metastatic transcriptional pattern revealed by gene expression profiling in primary colorectal carcinoma

D’Arrigo

Belluco

Ambrosi

et al. 2005

Intl Journal of Cancer

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Metastatic spread to the liver is the major contributor to mortality in patients with colorectal carcinoma (CRC). In order to seek for gene expression patterns associated with metastatic potential in primary CRC, we compared the transcriptional profiles of 10 radically resected primary CRCs from patients who did not develop distant metastases within a 5-year follow-up period with those of 10 primary/metastatic tumor pairs from patients with synchronous liver metastases. To focus selectively on neoplastic cells, the study was conducted on laser-microdissected bioptic tissues. Arrays of 7,864 human cDNAs were utilized. While a striking transcriptional similarity was observed between the primary tumors and their distant metastases, the nonmetastasizing primary tumors were clearly distinct from the primary/metastatic tumor pairs. Of 37 gene expression differences found between the 2 groups of primary tumors, 29 also distinguished nonmetastasizing tumors from metastases. The gene encoding for mannosyl (a-1,3-)-glycoprotein b-1,4-N-acetyl-glucosaminyl-transferase (GnT-IV) became significantly upregulated in primary/metastatic tumor pairs (p < 0.001). GnT-IV upregulation was confirmed by RT-PCR. These data support the existence of a specific transcriptional signature distinguishing primary colon adenocarcinomas with different metastatic potential, the further pursuit of which may lead to relevant clinical and therapeutic applications. ' 2005 Wiley-Liss, Inc.Key words: DNA microarray; metastasis; colorectal cancer Colorectal carcinoma (CRC) is the second leading cause of cancer deaths in developed countries.1 Metastatic spread, mostly to the liver, is the major cause of mortality in patients with this disease. Yet while the molecular events involved in the CRC adenoma-carcinoma sequence have been largely characterized, 2 little information is available on the mechanisms responsible for the metastatic phenotype. The identification in the primary tumors of molecular factors predictive of metastatic risk may have a relevant clinical impact, allowing for more personalized and effective treatment of CRC patients.Recent evidence based on gene expression profiling has shown that a metastatic fingerprint is detectable in the bulk of primary lung and breast tumors.3,4 On the other hand, no such metastatic signature has been demonstrated in CRC. A general problem related to gene expression studies in the oncologic field is the heterogeneous histology of the bioptic specimens that may contain, in addition to cancer cells, significant fractions of nonneoplastic tissue. Due to this heterogeneity, relevant changes in cancer cell gene expression may be easily overlooked.In order to seek for gene expression patterns specific to metastasis in CRC carcinoma, avoiding interference from nontumoral tissue, we combined laser microdissection of cancer cells and DNA microarray to compare the transcriptional profile of primary colon carcinomas both with that of patient-matched liver metastases and with that of a group of primary tumors of meta...

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Section: Resultsmentioning

confidence: 99%

“…The downregulation of p27Kip1 requires its interaction with components of the nuclear pore. 8,9 Thus, an increased expression of Nup50 might affect p27Kip1 degradation, thereby altering the control of cell proliferation. Among the downregulated genes, we found the growth arrestspecific gas7 gene.…”

Section: Discussionmentioning

confidence: 99%

Metastatic transcriptional pattern revealed by gene expression profiling in primary colorectal carcinoma

D’Arrigo

Belluco

Ambrosi

et al. 2005

Intl Journal of Cancer

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“…The pore association of Nup50 was further characterized by immunoelectron microscopy, which mapped Nup50 to the basket element of the nuclear pore complex (NPC), 3 in close proximity to Nup153 (5). Indeed, Nup50 and Nup153 were found to associate (4), and since then, Nup153 was determined to be essential for the nuclear pore localization of Nup50 (6). Interestingly, both of these nucleoporins are highly dynamic components of the NPC (7).…”

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confidence: 99%

“…Kip1 (3,4). The pore association of Nup50 was further characterized by immunoelectron microscopy, which mapped Nup50 to the basket element of the nuclear pore complex (NPC), 3 in close proximity to Nup153 (5).…”

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confidence: 99%

The Nup153-Nup50 Protein Interface and Its Role in Nuclear Import

Makise

Mackay

Elgort

et al. 2012

Journal of Biological Chemistry

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Background: An interaction network involving soluble factors and nuclear pore proteins underlies nucleocytoplasmic transport. Results: Nup50 interacts with two regions of Nup153, one of which is bridged by importin ␣. Conclusion: Efficient import is dependent on the interaction between Nup153 and Nup50. Significance: Nup153 provides a scaffold to facilitate interactions that contribute to trafficking through the nuclear pore.

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“…This pore protein plays roles in both import and export pathways (6 -11). Consistent with this, Nup153 interacts with various transport receptors (7,(12)(13)(14)(15)(16)(17)(18), as well as with specific cargo (6, 10). Nup153 has also been found to be essential for the localization of other pore components (19) and is specifically thought to anchor the basket constituent TPR (20).…”

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confidence: 57%

Sequence Preference in RNA Recognition by the Nucleoporin Nup153

Ball¹,

Dimaano²,

Bilak

et al. 2007

Journal of Biological Chemistry

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The vertebrate nuclear pore protein Nup153 contains a novel RNA binding domain. This 150-amino acid region was previously found to bind preferentially to a panel of mRNAs when compared with structured RNAs, such as tRNA, U snRNA, and double-stranded RNA. The ability to broadly recognize mRNA led to the conclusion that the Nup153 RNA binding domain confers a general affinity for single-stranded RNA. Here, we have probed Nup153 RNA recognition to decipher how this unique RNA binding domain discriminates between potential targets. We first mapped the binding determinant within an RNA fragment that associates relatively robustly with the Nup153 RNA binding domain. We next designed synthetic RNA oligonucleotides to systematically delineate the features within this minimal RNA fragment that are key to Nup153 RNA-binding domain binding and demonstrated that the binding preferences of Nup153 do not reflect general preferences of an mRNA/single-stranded RNA-binding protein. We further found that the association between Nup153 and a cellular mRNA can be attributed to an interaction with specific subregions of the RNA. These results indicate that Nup153 can discriminate between mRNA and other classes of RNA transcripts due in part to direct recognition of a loose sequence motif. This information adds a new dimension to the interfaces that can contribute to recognition in mRNA export cargo selection and fate.Nuclear pore complexes are macromolecular structures that bridge the inner and outer nuclear membranes to form a channel for nucleocytoplasmic traffic (1-3). Recent molecular characterization of pore complexes has revealed that they are comprised of only ϳ30 different proteins (4, 5), with multiples of eight copies of each protein forming the 8-fold symmetric structure characteristic of the nuclear pore complex. A small number of nucleoporins are restricted in localization to either the nuclear or cytoplasmic side of the pore, and their skewed distribution contributes to distinct features on each of these faces: the nuclear basket structure and the cytoplasmic filaments. The observation that repetitive arrangement of a relatively limited number of proteins creates the elaborate pore structure suggests that each nucleoporin carries out multiple tasks, from providing structural scaffolding to contacting diverse cargo-receptor complexes as they transit through the pore.The paradigm of multifunctional pore components is well illustrated by the nucleoporin Nup153. This pore protein plays roles in both import and export pathways (6 -11). Consistent with this, Nup153 interacts with various transport receptors (7,(12)(13)(14)(15)(16)(17)(18), as well as with specific cargo (6, 10). Nup153 has also been found to be essential for the localization of other pore components (19) and is specifically thought to anchor the basket constituent TPR (20). Somewhat paradoxically, Nup153 has been shown to be dynamically localized to the nuclear pore (21,22). This apparent contradiction, as well as the multiple roles implicated for Nup153, ma...

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Characterization and Targeted Disruption of Murine Nup50, a p27^Kip1-Interacting Component of the Nuclear Pore Complex

Cited by 105 publications

References 33 publications

Metastatic transcriptional pattern revealed by gene expression profiling in primary colorectal carcinoma

Metastatic transcriptional pattern revealed by gene expression profiling in primary colorectal carcinoma

The Nup153-Nup50 Protein Interface and Its Role in Nuclear Import

Sequence Preference in RNA Recognition by the Nucleoporin Nup153

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Characterization and Targeted Disruption of Murine Nup50, a p27Kip1-Interacting Component of the Nuclear Pore Complex

Cited by 105 publications

References 33 publications

Metastatic transcriptional pattern revealed by gene expression profiling in primary colorectal carcinoma

Metastatic transcriptional pattern revealed by gene expression profiling in primary colorectal carcinoma

The Nup153-Nup50 Protein Interface and Its Role in Nuclear Import

Sequence Preference in RNA Recognition by the Nucleoporin Nup153

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Characterization and Targeted Disruption of Murine Nup50, a p27^Kip1-Interacting Component of the Nuclear Pore Complex