A mutant nuclear protein with similarity to RNA binding proteins interferes with nuclear import in yeast.

Bossie, Mark; DeHoratius, C; Barcelo, Gail; Silver, Pamela A.

doi:10.1091/mbc.3.8.875

Cited by 118 publications

(158 citation statements)

References 68 publications

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“…HSS1 does not suppress the temperature-sensitivity of all sec63 mutations but is specific for the sec63-101 allele ( Figure 1B). HSS1 also does not suppress the temperature-sensitive phenotype of other ER translocation mutants ( Figure 1B), such as sec61-2, sec62-1, and kar2-159, or of npl4-1 (Bossie et al, 1992), another nuclear localization mutant.…”

Section: Specific Suppression Of Sec63-101 By Hss1mentioning

confidence: 90%

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Suppression of a sec63 mutation identifies a novel component of the yeast endoplasmic reticulum translocation apparatus.

Kurihara

Silver

1993

MBoC

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Mutations in the SEC63 gene are associated with defects in protein translocation into the endoplasmic reticulum (ER) as well as in nuclear protein localization in Saccharomyces cerevisiae. To identify proteins that might interact and/or function with SEC63p, we cloned a high copy suppressor (HSS1) of the temperature-sensitive lethal phenotype of the sec63-101 mutant. HSS1 is an allele-specific sec63 suppressor that encodes an integral ER membrane glycoprotein of 206 amino acids with the N-terminus in the ER lumen and C-terminal region in the cytoplasm. Haploid strains disrupted for HSS1 are temperature-sensitive for growth and accumulate precursor forms of Kar2p and invertase. The HSS1 null allele is synthetically lethal in combination with mutations affecting ER translocation. We propose that HSSlp is important for ER translocation and interacts with previously identified components of the yeast translocation apparatus. HSS1 is identical to SEC66, which encodes a glycoprotein complexed with SEC62p and SEC63p.

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Section: Specific Suppression Of Sec63-101 By Hss1mentioning

confidence: 90%

“…Judging by indirect immunofluorescence using antibodies directed against Npl3p, a normally nuclear protein (Bossie et al, 1992) Figure 5. A myc-tag was introduced at the C-terminus of Hsslp as described in MATERIALS AND METHODS.…”

Section: Specific Suppression Of Sec63-101 By Hss1mentioning

confidence: 99%

Suppression of a sec63 mutation identifies a novel component of the yeast endoplasmic reticulum translocation apparatus.

Kurihara

Silver

1993

MBoC

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“…We further analyzed the distribution of endogenous Nop1p (38) by indirect immunofluorescence microscopy. As representatives of a second class of nuclear proteins with noncanonical NLSs, we analyzed the distribution of endogenous Nab2p (39), Nab3p (40), Npl3p (33), and a normally nuclear fusion of Hrp1p (41) to GFP. Cells deleted for KAP123 also showed normal distribution of all nuclear proteins tested.…”

Section: Pse1 Is Essential For Growth and Has A Redundantmentioning

confidence: 99%

Importin/karyopherin protein family members required for mRNA export from the nucleus

Seedorf

Silver

1997

Proc. Natl. Acad. Sci. U.S.A.

131

124

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The yeast Saccharomyces cerevisiae contains three proteins (Kap104p, Pse1p, and Kap123p) that share similarity to the 95-kDa ␤ subunit of the nuclear transport factor importin (also termed karyopherin and encoded by KAP95͞RSL1 in yeast). Proteins that contain nuclear localization sequences are recognized in the cytoplasm and delivered to the nucleus by the heterodimeric importin complex. A second importin-related protein, transportin, delivers a subset of heterogeneous nuclear ribonucleoproteins (hnRNPs) to the nucleoplasm. We now show that in contrast to loss of importin ␤ (Kap95p͞Rsl1p) and transportin (Kap104p), conditional loss of Pse1p in a strain lacking Kap123p results in a specific block of mRNA export from the nucleus. Overexpression of Sxm1p, a protein related to Cse1p in yeast and to the human cellular apoptosis susceptibility protein, relieves the defects of cells lacking Pse1p and Kap123p. Thus, a major role of Pse1p, Kap123p, and Sxm1p may be nuclear export rather than import, suggesting a symmetrical relationship between these processes.Movement of macromolecules in and out of the nucleus is a highly regulated process essential for proper progression though the cell cycle, response to extracellular signals, and viral maturation. Our knowledge of the mechanism by which proteins are imported into and RNAs exported from the nucleus has grown significantly in recent years. Proteins have been identified that mediate both inward and outward macromolecular movement and both processes appear to be regulated by some of the same factors (reviewed in refs. 1 and 2).Import of proteins into the nucleus is a highly conserved, multistep process initiated by recognition of a nuclear localization sequence (NLS) by a cognate receptor, followed by docking of the complex at the nuclear pore, and GTPdependent translocation into the nucleoplasm. The receptor for the canonical NLS is a heterodimeric protein complex variously called importin or karyopherin, composed of an ␣ (NLS-binding) and a ␤ (docking) subunit (3-6). Translocation through the nuclear pore is driven by GTP hydrolysis, catalyzed by the small ras-related GTP-binding protein Ran and its regulators (7-10). Once inside the nucleus, the importin͞ karyopherin complex is probably dissociated and the transport factors recycled to the cytoplasm (5). This relatively simple model fails to explain the nuclear import of proteins that lack an NLS conforming to the canonical sequences. The recent identification of a role for the importin ␤ homolog transportin, in the nuclear import of heterogeneous nuclear ribonucleoprotein (hnRNP) A1 raised the possibility that different classes of nuclear proteins would be transported by different pathways, defined by the identity of the ␤ subunit involved (11, 12).In contrast to protein import, how RNAs are exported from the nucleus to the cytoplasm is less well understood. Nascent RNA is subject to a number of posttranscriptional modifications, and it seems likely that RNA moves through the nucleoplasm and the nuclear pore...

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“…npll is allelic to sec63 [78], a known gene required for translocation across the ER membrane; npll mutants are defective in nuclear retention rather than nuclear transport. Mutants of np13 [79] and np16 [lo] alter the uptake of proteins into the nucleus with no apparent defect in nuclear retention. NPL3 encodes a nuclear protein with a glycine/arginine rich sequence typically found in several nucleolar proteins, and an RNA binding sequence [79].…”

Section: Genetic Screens For Nuclear Transport Mutantsmentioning

confidence: 99%

“…Mutants of np13 [79] and np16 [lo] alter the uptake of proteins into the nucleus with no apparent defect in nuclear retention. NPL3 encodes a nuclear protein with a glycine/arginine rich sequence typically found in several nucleolar proteins, and an RNA binding sequence [79]. It was suggested that the mutant NPL3 protein could bind to components of the nuclear transport machinery thereby interfering with the import of other karyophiles.…”

Section: Genetic Screens For Nuclear Transport Mutantsmentioning

confidence: 99%

The nuclear pore complex

Hurt

1993

FEBS Letters

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Over the past years, significant progress has been made both in the analysis of the structural and molecular organization of the nuclear pore complex (NPC) and the mechanism of nuclear transport. In this minireview, I will focus on some of the recent developments in this field. Structural studies employing high resolution EM have revealed a detailed view of the three-dimensional organization of the NPC. In addition, an isolation procedure which yields highly enriched NPCs from yeast has given insight into the molecular complexity of the NPC organization. By biochemical, immunological and genetic approaches, a series of novel pore proteins were identified. Exploiting yeast as a genetic system, several mutants defective in nuclear import of proteins and export of RNA were selected. By in vitro nuclear transport assays, soluble cytoplasmic factors including NLS (nuclear localization sequence) binding proteins and heat shock proteins required for nuclear accumulation were found. The aim of the future research must be to put these various components of the NPC and nuclear transport machinery in a topological and functional context. Nuclear pore; Nuclear pore complex; Nuclear transport; Nuclear envelope; Nuclear localization sequence; Nucleoporin GENERAL OVERVIEWThe nucleus is surrounded by a double membrane which compartmentalizes nuclear and cytoplasmic reactions. Besides its key role in regulating nucleocytoplasmic transport, the nuclear membrane provides a structural support for the attachment of other macromolecular structures such as the nuclear lamina, nucleoskeleton, cytoskeleton and chromatin. Furthermore, the outer nuclear membrane, which is covered with ribosomes and continuous with the ER, is a site for protein synthesis and protein translocation.The transport of molecules and macromolecules across the nuclear membrane occurs through the nuclear pore complexes (NPCs). Several aspects of both the structural organization of the NPC and its role in nuclear transport reactions have been reviewed extensively [l-lo]. It has been estimated that up to one hundred proteins constitute the NPC. How these proteins are involved in the biogenesis and structural organization of the nuclear pore complex and in nucleocytoplasmic trafficking remains a challenging question for the next decade of research.For molecules to enter the cell nucleus, two mechanisms exist: passive diffusion of small molecules, and active transport of large macromolecules. The exclusion limit for diffusion is approximately 40-60 kDa [l 11. If large molecules have to enter the nucleus, they require active transport which is ATP and temperature depend- 76 ent [12]. However, even small and diffusable nuclear proteins such as histone Hl are actively imported into the nucleus [13,14].Targeting sequences on nuclear proteins are responsible for specific organelle sorting. One of the first nuclear targeting signals (NLS = nuclear localization sequence) to be identified was the short, 7 amino acid long sequence Pro-Lys-Lys-Lys-Arg-Lys-Val (PKKKRKV) of SV40 l...

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A mutant nuclear protein with similarity to RNA binding proteins interferes with nuclear import in yeast.

Cited by 118 publications

References 68 publications

Suppression of a sec63 mutation identifies a novel component of the yeast endoplasmic reticulum translocation apparatus.

Suppression of a sec63 mutation identifies a novel component of the yeast endoplasmic reticulum translocation apparatus.

Importin/karyopherin protein family members required for mRNA export from the nucleus

The nuclear pore complex

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