PMID- 10551826
OWN - NLM
STAT- MEDLINE
DCOM- 20000103
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 46
DP  - 1999 Nov 12
TI  - A bipartite nuclear localization signal is required for p53 nuclear import
      regulated by a carboxyl-terminal domain.
PG  - 32699-703
AB  - Abnormal p53 cellular localization has been considered to be one of the
      mechanisms that could inactivate p53 function. To understand the regulation of
      p53 cellular trafficking, we have previously identified two p53 domains involved 
      in its localization. A basic domain, Lys(305)-Arg(306), is required for p53
      nuclear import, and a carboxyl-terminal domain, namely the cytoplasmic
      sequestration domain (CSD) from residues 326-355, could block the nuclear import 
      of Lys(305) or Arg(306) mutated p53. To characterize further the function of
      these two domains, we demonstrate in this report that the previously described
      major nuclear localization signal works together with Lys(305)-Arg(306) to form a
      bipartite and functional nuclear localization sequence (NLS) for p53 nuclear
      import. The CSD could block the binding of p53 to the NLS receptor, importin
      alpha, and reduce the efficiency of p53 nuclear import in MCF-7, H1299, and
      Saos-2 cells. The blocking effect of the CSD is not due to the enhancement of
      nuclear export or oligomerization of the p53. These results indicate that the CSD
      can regulate p53 nuclear import by controlling access of the NLS to importin
      alpha binding.
FAU - Liang, S H
AU  - Liang SH
AD  - Department of Internal Medicine, University of Michigan Medical Center, Ann
      Arbor, Michigan 48109-0936, USA.
FAU - Clarke, M F
AU  - Clarke MF
LA  - eng
GR  - CA67140/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Antigens, Polyomavirus Transforming)
RN  - 0 (Nuclear Localization Signals)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 0 (alpha Karyopherins)
SB  - IM
MH  - Amino Acid Sequence
MH  - Antigens, Polyomavirus Transforming/genetics
MH  - Cell Line
MH  - Cell Nucleus/metabolism
MH  - Humans
MH  - Molecular Sequence Data
MH  - Mutagenesis
MH  - Nuclear Localization Signals/*genetics
MH  - Nuclear Proteins/metabolism
MH  - Protein Binding/genetics
MH  - Protein Conformation
MH  - Transfection
MH  - Tumor Cells, Cultured
MH  - Tumor Suppressor Protein p53/*chemistry/genetics
MH  - alpha Karyopherins
EDAT- 1999/11/07 00:00
MHDA- 1999/11/07 00:01
CRDT- 1999/11/07 00:00
PHST- 1999/11/07 00:00 [pubmed]
PHST- 1999/11/07 00:01 [medline]
PHST- 1999/11/07 00:00 [entrez]
AID - 10.1074/jbc.274.46.32699 [doi]
AID - S0021-9258(17)46565-3 [pii]
PST - ppublish
SO  - J Biol Chem. 1999 Nov 12;274(46):32699-703. doi: 10.1074/jbc.274.46.32699.