2010
DOI: 10.1101/gad.1873910
|View full text |Cite
|
Sign up to set email alerts
|

Isoform-specific p73 knockout mice reveal a novel role for ΔNp73 in the DNA damage response pathway

Abstract: Mice with a complete deficiency of p73 have severe neurological and immunological defects due to the absence of all TAp73 and DNp73 isoforms. As part of our ongoing program to distinguish the biological functions of these isoforms, we generated mice that are selectively deficient for the DNp73 isoform. Mice lacking DNp73 (DNp73 -/-mice) are viable and fertile but display signs of neurodegeneration. Cells from DNp73 -/-mice are sensitized to DNA-damaging agents and show an increase in p53-dependent apoptosis. W… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
2
1
1

Citation Types

10
207
1
1

Year Published

2011
2011
2024
2024

Publication Types

Select...
8

Relationship

1
7

Authors

Journals

citations
Cited by 190 publications
(219 citation statements)
references
References 46 publications
10
207
1
1
Order By: Relevance
“…Trp73 is a member of Trp53 family gene, known to produce tumor-suppressive TAp73, or oncogenic DNp73 isoforms (Tomasini et al, 2008;Wilhelm et al, 2010). DNp73 deficiency sensitizes cells to DNA damage, increases the levels of p53 and its target genes and consequently, enhances p53-mediated apoptosis (Wilhelm et al, 2010). In line with above results, DNp73 À/À immortalized MEFs exhibited a reduction in DJ-1 protein levels as compared with DNp73 þ / þ MEFs.…”
Section: Dj-1/p53 Connection During Cell Transformation S Vasseur Et Alsupporting
confidence: 69%
See 2 more Smart Citations
“…Trp73 is a member of Trp53 family gene, known to produce tumor-suppressive TAp73, or oncogenic DNp73 isoforms (Tomasini et al, 2008;Wilhelm et al, 2010). DNp73 deficiency sensitizes cells to DNA damage, increases the levels of p53 and its target genes and consequently, enhances p53-mediated apoptosis (Wilhelm et al, 2010). In line with above results, DNp73 À/À immortalized MEFs exhibited a reduction in DJ-1 protein levels as compared with DNp73 þ / þ MEFs.…”
Section: Dj-1/p53 Connection During Cell Transformation S Vasseur Et Alsupporting
confidence: 69%
“…Endogenous p53 represses DJ-1 in a cell-type independent manner. (a-c) Wild-type, p53 À/À and DNp73 À/À primary or immortalized MEFs were derived from gene-targeted C57BL6/J background mice and their littermates as previously described (Vasseur et al, 2002;Wilhelm et al, 2010). Transformed MEFs were obtained by transduction with the E1A and RasV12 oncogenes using retroviral infection (pLPC-E1A-IRES-RasV12) and selected by growth in puromycin.…”
Section: Resultsmentioning
confidence: 99%
See 1 more Smart Citation
“…33,34 Moreover, they also have a reduction in cortical thickness as a consequence of loss of mature cortical neurons. 35 Recently, it has been demonstrated that TAp73 expression increases in parallel with neuronal differentiation, and its ectopic expression induces neurite outgrowth and expression of neuronal markers in neuroblastoma cell lines, suggesting that it has a pro-differentiation role. 20 In particular, TAp73 acts, at least in part, through microRNA-34a to regulate neuronal differentiation.…”
Section: Introductionmentioning
confidence: 99%
“…Consistently, DNp73 À / À mouse embryonic fibroblasts were found to be sensitized to genotoxic stresses and showed enhanced p53-dependent apoptosis, indicating that DNp73 is a critical inhibitor of apoptosis. 7 Not surprisingly, DNp73 expression is frequently elevated in many human cancers, including lung, neuroblastoma, colon, ovarian, liver, etc., [8][9][10] which suggests a role in either promoting cellular growth or inhibiting apoptosis, as well as in affecting chemosensitivity. In the latter context, TAp73 and p53 are activated by a multitude of chemotherapeutic agents, 11 linking their functions to the chemosensitivity of cancer cells.…”
mentioning
confidence: 99%