Antibodies to Asp-Asp-Glu-Asp Can Inhibit Transport of Nuclear Proteins into the Nucleus

Yoneda, Yoshihiro; Imamoto-Sonobe, Naoko; Matsuoka, Yosuke; Iwamoto, Ryo; Kiho, Yukio; Uchida, Tsuyoshi

doi:10.1126/science.3051382

Cited by 84 publications

(42 citation statements)

References 26 publications

(7 reference statements)

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“…Antibodies against negatively charged polypeptides block the transport of SV40 T antigen into the nucleus in various cells, including mouse fibroblasts (Yoneda et al 1988). This suggests that wild-type SV40 T antigen may be transported to the nucleus by a charge-sensitive receptor molecule that recognizes a nuclear signal sequence on the T-antigen molecule.…”

Section: Discussionmentioning

confidence: 99%

“…In rat liver, SV40 T antigen transport to the nucleus is mediated by an ATP-dependent active transport system (Markland et al 1987). Microinjection of antibodies raised against negatively charged peptides (Asp-Asp-Glu-Asp) inhibits nuclear transport of SV40 T antigen in a variety of cell lines (Yoneda et al 1988), suggesting that the cellular molecules involved in nuclear transport can be modulated experimentally. Deletion or mutation of the region of the T-antigen gene encoding the nuclear localization signal damages the capacity of mouse, hamster, and monkey cells to transport T antigen to the nucleus (Lanford andButel 1982, 1984;Kalderon et al 1984a, b;Alfano and McMacken 1989).…”

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confidence: 99%

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Human major HSP70 protein complements the localization and functional defects of cytoplasmic mutant SV40 T antigen in Swiss 3T3 mouse fibroblast cells.

Jeoung

Chen²,

Windsor³

et al. 1991

Genes & Development

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The CT3 cytoplasmic localization mutant of SV40 T antigen is neither properly transported to the nucleus nor is it functional in rodent cells. Human precrisis cells are able to complement this mutation, as they are fully transformed by CT3 with wild-type efficiency. The human-specific factors responsible for this species-specific difference in response to CT3 were localized to human chromosome 6 by synteny in a panel of six somatic cell hybrids. A major human HSP70 heat shock protein located on chromosome 6 is expressed constitutively in human cells. Hsp70 proteins have been reported to play a role in intracellular movement of newly synthesized proteins. To test whether human HSP70 played a role in the complementation by human cells of the defect of CT3, we constructed a series of mouse cell lines expressing human HSP70 and tested them for their ability to localize CT3 T antigen in the nucleus and for their ability to be transformed by CT3 DNA. Mouse cell lines expressing human HSP70 protein were able to translocate mutant CT3 T antigen into the nucleus and were transformed by CT3 at rates comparable with wild-type SV40. Mouse-inducible HSP70 protein was not able to translocate cytoplasmic T antigen in Swiss 3T3 mouse fibroblast cells, even after heat shock. Apparently human HSP70 is capable of complementing directly or indirectly the structural and functional alterations in SV40 T antigen introduced by the CT3 mutation.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Human major HSP70 protein complements the localization and functional defects of cytoplasmic mutant SV40 T antigen in Swiss 3T3 mouse fibroblast cells.

Jeoung

Chen²,

Windsor³

et al. 1991

Genes & Development

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“…Recently, Yoneda et al [33] suggested that the binding pocket of the putative nuclear signal receptor in nuclear pores contains numerous acidic residues that interact in a complementary fashion with the basic residues of the NLS sequence. They raised an antibody against a synthetic peptide, D-D-D-E-D, which is complementary to the NLS sequence of the SV40 large-T signal peptide and found that on microinjection into cultured cells, this anti-peptide antibody bound to nuclear envelopes and blocked NLS-mediated uptake of proteins into the nucleus.…”

Section: Acidic Amino Acid Clusters and Tyrosine Phosphorylation Sitementioning

confidence: 99%

Possible mechanism of nuclear translocation of proteasomes

et al. 1990

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Proteasomes (multicatalytic proteinase complexes), which are identical to the ubiquitous eukaryotic 20S particles, are localized in both the cytoplasm and the nucleus, but the mechanism of their co‐localization in the two compartments is unknown. On examination of the primary structures of subunits of proteasomes, a consensus sequence for nuclear translocation of proteins, X‐X‐K‐K(R)‐X‐K(R) (where X is any residue), was found to be present in some subunits and to be highly conserved in the subunits of a wide range of eukaryotes. In addition, proteasomal subunits were found to bear a cluster of acidic amino acid residues and also a potential tyrosine phosphorylation site that was located in the same polypeptide chain as the nuclear location signal. These structural properties suggest that two sets of clusters with positive and negative charges serve to regulate the translocation of proteasomes from the cytoplasm to the nucleus, and that phosphorylation of tyrosine in certain subunits may play an additional role in transfer of proteasomes into the nucleus.

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“…binding proteins (Yoneda et al, 1988;Adam et al, 1989;Benditt et al, 1989;Li and Thomas, 1989;Lee and M616se, 1989;Silver et al, 1989) have also recently been identified, although their specificity and subcellular location remain unclear. It is well documented that the specificity of nuclear protein import is determined by the NLS .…”

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confidence: 99%

p34cdc2-mediated phosphorylation at T124 inhibits nuclear import of SV-40 T antigen proteins.

Jans

Ackermann

Bischoff

et al. 1991

The Journal of Cell Biology

198

203

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Abstract. The nuclear import of transcription regulatory proteins appears to be used by the cell to trigger transitions in cell cycle, morphogenesis, and transformation . We have previously observed that the rate at which SV-40 T antigen fusion proteins containing a functional nuclear localization sequence (NLS; residues 126-132) are imported into the nucleus is enhanced in the presence of the casein kinase R (CK-II) site Si"ai2 . In this study purified p34cdc2 kinase was used to phosphorylate T antigen proteins specifically at T'24 and kinetic measurements at the single-cell level performed to assess its effect on nuclear protein import . Tí24 phosphorylation, which could be functionally simulated by a T-to-13 124 substitution, was found to reduce the maximal extent of nuclear accumulation whilst negligibly affecting the import C LOSE correlations between the nuclear cytoplasmic distribution ofcertain transcription factors (Lenardo and

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Antibodies to Asp-Asp-Glu-Asp Can Inhibit Transport of Nuclear Proteins into the Nucleus

Cited by 84 publications

References 26 publications

Human major HSP70 protein complements the localization and functional defects of cytoplasmic mutant SV40 T antigen in Swiss 3T3 mouse fibroblast cells.

Human major HSP70 protein complements the localization and functional defects of cytoplasmic mutant SV40 T antigen in Swiss 3T3 mouse fibroblast cells.

Possible mechanism of nuclear translocation of proteasomes

p34cdc2-mediated phosphorylation at T124 inhibits nuclear import of SV-40 T antigen proteins.

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