PMID- 10391251
OWN - NLM
STAT- MEDLINE
DCOM- 19990721
LR  - 20161124
IS  - 0028-0836 (Print)
IS  - 0028-0836 (Linking)
VI  - 399
IP  - 6738
DP  - 1999 Jun 24
TI  - p73 is regulated by tyrosine kinase c-Abl in the apoptotic response to DNA
      damage.
PG  - 814-7
AB  - The protein p73 is a structural and functional homologue of the p53
      tumour-suppressor protein but, unlike p53, it is not induced in response to DNA
      damage. The tyrosine kinase c-Abl is activated by certain DNA-damaging agents and
      contributes to the induction of programmed cell death (apoptosis) by
      p53-dependent and p53-independent mechanisms. Here we show that c-Abl binds to
      p73 in cells, interacting through its SH3 domain with the carboxy-terminal
      homo-oligomerization domain of p73. c-Abl phosphorylates p73 on a tyrosine
      residue at position 99 both in vitro and in cells that have been exposed to
      ionizing radiation. Our results show that c-Abl stimulates p73-mediated
      transactivation and apoptosis. This regulation of p73 by c-Abl in response to DNA
      damage is also demonstrated by a failure of ionizing-radiation-induced apoptosis 
      after disruption of the c-Abl-p73 interaction. These findings show that p73 is
      regulated by a c-Abl-dependent mechanism and that p73 participates in the
      apoptotic response to DNA damage.
FAU - Yuan, Z M
AU  - Yuan ZM
AD  - Department of Cancer Cell Biology, Harvard School of Public Health, Dana Farber
      Cancer Institute, Boston, Massachusetts 02115, USA.
FAU - Shioya, H
AU  - Shioya H
FAU - Ishiko, T
AU  - Ishiko T
FAU - Sun, X
AU  - Sun X
FAU - Gu, J
AU  - Gu J
FAU - Huang, Y Y
AU  - Huang YY
FAU - Lu, H
AU  - Lu H
FAU - Kharbanda, S
AU  - Kharbanda S
FAU - Weichselbaum, R
AU  - Weichselbaum R
FAU - Kufe, D
AU  - Kufe D
LA  - eng
PT  - Journal Article
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Trp73 protein, mouse)
RN  - 0 (Tumor Protein p73)
RN  - 0 (Tumor Suppressor Proteins)
RN  - EC 2.7.10.2 (Proto-Oncogene Proteins c-abl)
SB  - IM
CIN - Nature. 1999 Jun 24;399(6738):734-5, 737. PMID: 10391235
EIN - Nature 1999 Aug 19;400(6746):792
MH  - Animals
MH  - *Apoptosis
MH  - Binding Sites
MH  - COS Cells
MH  - Cell Line
MH  - *DNA Damage
MH  - DNA-Binding Proteins/*metabolism
MH  - Genes, Tumor Suppressor
MH  - Mice
MH  - Nuclear Proteins/*metabolism
MH  - Phosphorylation
MH  - Protein Binding
MH  - Proto-Oncogene Proteins c-abl/*metabolism
MH  - Recombinant Proteins/metabolism
MH  - Tumor Protein p73
MH  - Tumor Suppressor Proteins
MH  - src Homology Domains
EDAT- 1999/07/03 10:00
MHDA- 2001/03/23 10:01
CRDT- 1999/07/03 10:00
PHST- 1999/07/03 10:00 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1999/07/03 10:00 [entrez]
AID - 10.1038/21704 [doi]
PST - ppublish
SO  - Nature. 1999 Jun 24;399(6738):814-7. doi: 10.1038/21704.