PMID- 10570174
OWN - NLM
STAT- MEDLINE
DCOM- 20000106
LR  - 20220224
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 96
IP  - 24
DP  - 1999 Nov 23
TI  - Truncated BRCA2 is cytoplasmic: implications for cancer-linked mutations.
PG  - 13920-5
AB  - BRCA2 mutations predispose carriers mainly to breast cancer. The vast majority of 
      BRCA2 mutations are predicted to result in a truncated protein product. The 
      smallest known cancer-associated deletion removes from the C terminus only 224 of 
      the 3,418 residues constituting BRCA2, suggesting that these terminal amino acids 
      are crucial for BRCA2 function. A series of green fluorescent protein 
      (GFP)-tagged BRCA2 deletion mutants revealed that nuclear localization depends on 
      two nuclear localization signals that reside within the final 156 residues of 
      BRCA2. Consistent with this observation, an endogenous truncated BRCA2 mutant 
      (6174delT) was found to be cytoplasmic. Together, these studies provide a simple 
      explanation for why the vast majority of BRCA2 mutants are nonfunctional: they do 
      not translocate into the nucleus.
FAU - Spain, B H
AU  - Spain BH
AD  - Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA 
      92037, USA.
FAU - Larson, C J
AU  - Larson CJ
FAU - Shihabuddin, L S
AU  - Shihabuddin LS
FAU - Gage, F H
AU  - Gage FH
FAU - Verma, I M
AU  - Verma IM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (BRCA2 Protein)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Nuclear Localization Signals)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - BRCA2 Protein
MH  - Breast Neoplasms/*genetics
MH  - Cell Line, Transformed
MH  - Cell Nucleus/metabolism
MH  - Cytoplasm/metabolism
MH  - Female
MH  - Humans
MH  - Neoplasm Proteins/*genetics/metabolism
MH  - Nuclear Localization Signals
MH  - Recombinant Fusion Proteins/genetics/metabolism
MH  - Sequence Deletion
MH  - Transcription Factors/*genetics/metabolism
MH  - Tumor Cells, Cultured
PMC - PMC24166
EDAT- 1999/11/26 00:00
MHDA- 1999/11/26 00:01
CRDT- 1999/11/26 00:00
PHST- 1999/11/26 00:00 [pubmed]
PHST- 1999/11/26 00:01 [medline]
PHST- 1999/11/26 00:00 [entrez]
AID - 4266 [pii]
AID - 10.1073/pnas.96.24.13920 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1999 Nov 23;96(24):13920-5. doi: 
      10.1073/pnas.96.24.13920.