Pentapeptide nuclear localization signal in adenovirus E1a.

Lyons, Robert H.; Ferguson, B; Rosenberg, Martin

doi:10.1128/mcb.7.7.2451

Cited by 158 publications

(85 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The two Ela sequences differ slightly, and only the adenovirus type 2/5 sequence has been previously investigated for nuclear targeting ability (16). A peptide based on the eight C-terminal amino acids of Ela from adenovirus type 7 (P10) was only marginally able to target CSA to the nucleus following microinjection into the cytoplasm (Table 1 and Fig.…”

Section: Methodsmentioning

confidence: 99%

“…A peptide, P8, based on this second site was able to target CSA to the nucleus but much less effectively than peptide P2 (Table 1 and Fig. 1 In addition, fusion of the five C-terminal residues of Ela to the C terminus of galactokinase causes the resulting recombinant protein to be localized in the nucleus (16). A synthetic peptide (P6) containing the eight C-terminal adenovirus type 2/5 protein Ela residues was very effective at targeting CSA to the nucleus (Table 1).…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Sequence requirements for synthetic peptide-mediated translocation to the nucleus.

Chelsky¹,

Ralph²,

Jonak³

1989

Mol. Cell. Biol.

391

221

View full text Add to dashboard Cite

The abilities of 18 synthetic peptides to target a carrier protein to the nucleus following microinjection into the cytoplasm of HeLa cells were determined. Eight of the sequences chosen for synthesis were based on published nuclear targeting regions as determined by gene fusion and deletion experiments. Six of these sequences were found to be effective when mimicked by a synthetic peptide and conjugated to a carrier protein.One additional peptide was based on a region of lamin L,, a nuclear protein from Xenopus laevis, in which the nuclear targeting region had not been previously investigated. This peptide was also able to target a carrier protein to the nucleus. Eight other peptides which resemble the known targeting signals had little or no nuclear targeting ability. Peptides which were able to target a carrier protein to the nucleus did so within 45 min of injection into the cytoplasm. Two peptides with little or no apparent nuclear targeting ability after 45 min were examined for longer times as well. No increase in nuclear accumulation was observed between 45 min and 4 h after cytoplasmic injection. Comparison of the sequences which were effective at nuclear targeting with those that were not revealed a possible consensus sequence for peptide-mediated nuclear transport.Proteins destined for the nucleus in eucaryotic cells enter through large pore structures distributed evenly over the nuclear envelope. Entry An alternative to genetic manipulation has been chemical synthesis of a peptide which mimics a putative nuclear targeting region. The nuclear targeting sequence of the simian virus 40 (SV40) T antigen has been synthesized and cross-linked to a variety of nonnuclear carrier proteins, such as serum albumin, immunoglobulin G, and ferritin. These conjugates are translocated to the nucleus following microinjection into the cytoplasm of cells (6,14). Changing one amino acid in the sequence (lysine 128 to either threonine or asparagine) yields a dramatic reduction in the degree of transport of the peptide conjugate into nuclei (6, 14). The results of these peptide "'mutations" are consistent with results obtained by mutational analysis of the T antigen itself (10, 13).We synthesized 2 SV40 T-antigen nuclear targeting peptides and 16 others to determine the general utility of peptide-mediated translocation and to define further the sequence requirements for nuclear transport. We found that some but not all of the genetically defined transport sequences could be mimicked by peptide conjugates. Although all of the peptides capable of directing nuclear transport contain a cluster of basic residues, this in itself is not * Corresponding author. sufficient for transport. Most of the nontargeting peptides also contain either three or four basic residues clustered in a short sequence. A comparison of the amino acid sequences of nuclear targeting versus nontargeting peptides has led us to propose a consensus sequence for such peptides. MATERIALS AND METHODSPeptide synthesis. All of the peptides listed in Table 1 wer...

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Sequence requirements for synthetic peptide-mediated translocation to the nucleus.

Chelsky¹,

Ralph²,

Jonak³

1989

Mol. Cell. Biol.

391

221

View full text Add to dashboard Cite

show abstract

“…How E1A acetylation relates to E1A's ability to mediate viral replication and cellular transformation, awaits further investigation. Interestingly, Lys-239, comprises part of the E1A nuclear localization signal (NLS- Lyons et al, 1987). Acetylation of E1A might therefore, also regulate E1A localization.…”

Section: Exon 2 Functionsmentioning

confidence: 99%

Adenovirus E1A: remodelling the host cell, a life or death experience

2001

View full text Add to dashboard Cite

show abstract

“…Truncation of this sequence to the pentapeptide KRPRP is suffi cient to retain nuclear accumulation of an attached cargo to the same extent as the native E1a sequence. 54 The human c-myc protein also contains 2 regions that are able to target the nucleus. C-myc is a short-lived phosphoprotein found in the nucleus that is 439 amino acids in length.…”

Section: Nuclear Localization Signal Sequences For Protein Deliverymentioning

confidence: 99%

Peptide-guided gene delivery

Martin

Rice

2007

AAPS J

302

236

View full text Add to dashboard Cite

Although currently less effi cient than their viral counterparts, nonviral vectors are under intense investigation as a safer alternative for gene therapy. For successful delivery, the nonviral vector must be able to overcome many barriers to protect DNA and specifi cally deliver it for effi cient gene expression in target cells. The use of peptides as gene delivery vectors is advantageous over other nonviral agents in that they are able to achieve all of these goals. This review will focus on the application of peptides to mediate nonviral gene delivery. By examining the literature over the past 20 years, it becomes clear that no other class of biomolecules are simultaneously capable of DNA condensation, blocking metabolism, endosomal escape, nuclear localization, and receptor targeting. Based on virtually limitless diversity of peptide sequence and function information from nature, it is increasingly clear that peptide-guided gene delivery is still in its infancy.

show abstract

Pentapeptide nuclear localization signal in adenovirus E1a.

Cited by 158 publications

References 17 publications

Sequence requirements for synthetic peptide-mediated translocation to the nucleus.

Sequence requirements for synthetic peptide-mediated translocation to the nucleus.

Adenovirus E1A: remodelling the host cell, a life or death experience

Peptide-guided gene delivery

Contact Info

Product

Resources

About