Search: onr:"swepub:oai:prod.swepub.kib.ki.se:120174881" >
Isoform-specific p7...
Isoform-specific p73 knockout mice reveal a novel role for delta Np73 in the DNA damage response pathway
-
Wilhelm, MT (author)
-
Rufini, A (author)
-
Wetzel, MK (author)
-
show more...
-
Tsuchihara, K (author)
-
Inoue, S (author)
-
Tomasini, R (author)
-
Itie-Youten, A (author)
-
Wakeham, A (author)
-
- Arsenian-Henriksson, M (author)
- Karolinska Institutet
-
Melino, G (author)
-
Kaplan, DR (author)
-
Miller, FD (author)
-
Mak, TW (author)
-
show less...
-
(creator_code:org_t)
- 2010-03-01
- 2010
- English.
-
In: Genes & development. - : Cold Spring Harbor Laboratory. - 1549-5477 .- 0890-9369. ; 24:6, s. 549-560
- Related links:
-
http://genesdev.cshl...
-
show more...
-
http://kipublication...
-
https://doi.org/10.1...
-
show less...
Abstract
Subject headings
Close
- Mice with a complete deficiency of p73 have severe neurological and immunological defects due to the absence of all TAp73 and ΔNp73 isoforms. As part of our ongoing program to distinguish the biological functions of these isoforms, we generated mice that are selectively deficient for the ΔNp73 isoform. Mice lacking ΔNp73 (ΔNp73−/− mice) are viable and fertile but display signs of neurodegeneration. Cells from ΔNp73−/− mice are sensitized to DNA-damaging agents and show an increase in p53-dependent apoptosis. When analyzing the DNA damage response (DDR) in ΔNp73−/− cells, we discovered a completely new role for ΔNp73 in inhibiting the molecular signal emanating from a DNA break to the DDR pathway. We found that ΔNp73 localizes directly to the site of DNA damage, can interact with the DNA damage sensor protein 53BP1, and inhibits ATM activation and subsequent p53 phosphorylation. This novel finding may explain why human tumors with high levels of ΔNp73 expression show enhanced resistance to chemotherapy.
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
To the university's database
- By the author/editor
-
Wilhelm, MT
-
Rufini, A
-
Wetzel, MK
-
Tsuchihara, K
-
Inoue, S
-
Tomasini, R
-
show more...
-
Itie-Youten, A
-
Wakeham, A
-
Arsenian-Henriks ...
-
Melino, G
-
Kaplan, DR
-
Miller, FD
-
Mak, TW
-
show less...
- Articles in the publication
-
Genes & developm ...
- By the university
-
Karolinska Institutet