Sequence requirement for nuclear localization and growth inhibition of p27Kip1R, a degradation-resistant isoform of p27Kip1

Katsuya Hirano, Ying Zeng, Mayumi Hirano, Junji Nishimura, Hideo Kanaide

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

p27Kip1R is an isoform of p27Kip1, having a distinct C-terminus. The sequences of p27Kip1R required for nuclear localization and growth inhibition were determined in HeLa cells using a green fluorescence protein (GFP) as a reporter molecule. Region 153-168 and residues K168 and I169 were determined to play a critical role in the nuclear localization of p27Kip1R. Aliphatic amino acid was found to be a substitute for the basic residue in the typical nuclear localization signal, while its functional substitution was incomplete, thereby causing a significant cytoplasmic retention of p27Kip1R. p27Kip1R is thus the first example of an atypical bipartite nuclear localization signal with aliphatic amino acid as a functional residue. Despite cytoplasmic retention, p27Kip1R inhibited the cell growth as well as p27Kip1, while GFP alone had no effect. The mutants lacking an N-terminus containing the binding regions for cyclins and cyclin-dependent kinases also showed a significant degree of nuclear localization, but failed to inhibit cell growth. The growth inhibition by p27Kip1R as well as p27Kip1 was thus suggested to originate in the common N-terminal region.

Original languageEnglish
Pages (from-to)191-202
Number of pages12
JournalJournal of Cellular Biochemistry
Volume89
Issue number1
DOIs
Publication statusPublished - May 1 2003

Fingerprint

Cell growth
Protein Isoforms
Fluorescence
Amino Acids
Degradation
Nuclear Localization Signals
Cyclins
Cyclin-Dependent Kinases
Growth
Proteins
Substitution reactions
Fatty Acids
Molecules
HeLa Cells

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Sequence requirement for nuclear localization and growth inhibition of p27Kip1R, a degradation-resistant isoform of p27Kip1. / Hirano, Katsuya; Zeng, Ying; Hirano, Mayumi; Nishimura, Junji; Kanaide, Hideo.

In: Journal of Cellular Biochemistry, Vol. 89, No. 1, 01.05.2003, p. 191-202.

Research output: Contribution to journalArticle

@article{23179bd9205145cb9217fd972aa6df00,
title = "Sequence requirement for nuclear localization and growth inhibition of p27Kip1R, a degradation-resistant isoform of p27Kip1",
abstract = "p27Kip1R is an isoform of p27Kip1, having a distinct C-terminus. The sequences of p27Kip1R required for nuclear localization and growth inhibition were determined in HeLa cells using a green fluorescence protein (GFP) as a reporter molecule. Region 153-168 and residues K168 and I169 were determined to play a critical role in the nuclear localization of p27Kip1R. Aliphatic amino acid was found to be a substitute for the basic residue in the typical nuclear localization signal, while its functional substitution was incomplete, thereby causing a significant cytoplasmic retention of p27Kip1R. p27Kip1R is thus the first example of an atypical bipartite nuclear localization signal with aliphatic amino acid as a functional residue. Despite cytoplasmic retention, p27Kip1R inhibited the cell growth as well as p27Kip1, while GFP alone had no effect. The mutants lacking an N-terminus containing the binding regions for cyclins and cyclin-dependent kinases also showed a significant degree of nuclear localization, but failed to inhibit cell growth. The growth inhibition by p27Kip1R as well as p27Kip1 was thus suggested to originate in the common N-terminal region.",
author = "Katsuya Hirano and Ying Zeng and Mayumi Hirano and Junji Nishimura and Hideo Kanaide",
year = "2003",
month = "5",
day = "1",
doi = "10.1002/jcb.10499",
language = "English",
volume = "89",
pages = "191--202",
journal = "Journal of Cellular Biochemistry",
issn = "0730-2312",
publisher = "Wiley-Liss Inc.",
number = "1",

}

TY - JOUR

T1 - Sequence requirement for nuclear localization and growth inhibition of p27Kip1R, a degradation-resistant isoform of p27Kip1

AU - Hirano, Katsuya

AU - Zeng, Ying

AU - Hirano, Mayumi

AU - Nishimura, Junji

AU - Kanaide, Hideo

PY - 2003/5/1

Y1 - 2003/5/1

N2 - p27Kip1R is an isoform of p27Kip1, having a distinct C-terminus. The sequences of p27Kip1R required for nuclear localization and growth inhibition were determined in HeLa cells using a green fluorescence protein (GFP) as a reporter molecule. Region 153-168 and residues K168 and I169 were determined to play a critical role in the nuclear localization of p27Kip1R. Aliphatic amino acid was found to be a substitute for the basic residue in the typical nuclear localization signal, while its functional substitution was incomplete, thereby causing a significant cytoplasmic retention of p27Kip1R. p27Kip1R is thus the first example of an atypical bipartite nuclear localization signal with aliphatic amino acid as a functional residue. Despite cytoplasmic retention, p27Kip1R inhibited the cell growth as well as p27Kip1, while GFP alone had no effect. The mutants lacking an N-terminus containing the binding regions for cyclins and cyclin-dependent kinases also showed a significant degree of nuclear localization, but failed to inhibit cell growth. The growth inhibition by p27Kip1R as well as p27Kip1 was thus suggested to originate in the common N-terminal region.

AB - p27Kip1R is an isoform of p27Kip1, having a distinct C-terminus. The sequences of p27Kip1R required for nuclear localization and growth inhibition were determined in HeLa cells using a green fluorescence protein (GFP) as a reporter molecule. Region 153-168 and residues K168 and I169 were determined to play a critical role in the nuclear localization of p27Kip1R. Aliphatic amino acid was found to be a substitute for the basic residue in the typical nuclear localization signal, while its functional substitution was incomplete, thereby causing a significant cytoplasmic retention of p27Kip1R. p27Kip1R is thus the first example of an atypical bipartite nuclear localization signal with aliphatic amino acid as a functional residue. Despite cytoplasmic retention, p27Kip1R inhibited the cell growth as well as p27Kip1, while GFP alone had no effect. The mutants lacking an N-terminus containing the binding regions for cyclins and cyclin-dependent kinases also showed a significant degree of nuclear localization, but failed to inhibit cell growth. The growth inhibition by p27Kip1R as well as p27Kip1 was thus suggested to originate in the common N-terminal region.

UR - http://www.scopus.com/inward/record.url?scp=0037405203&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037405203&partnerID=8YFLogxK

U2 - 10.1002/jcb.10499

DO - 10.1002/jcb.10499

M3 - Article

C2 - 12682919

AN - SCOPUS:0037405203

VL - 89

SP - 191

EP - 202

JO - Journal of Cellular Biochemistry

JF - Journal of Cellular Biochemistry

SN - 0730-2312

IS - 1

ER -