Functional characterization of p53 pathway components in the ancient metazoan Trichoplax adhaerens.
The identification of genes encoding a p53 family member and an Mdm2 ortholog in the ancient placozoan Trichoplax adhaerens advocates for the evolutionary conservation of a pivotal stress-response pathway observed in all higher eukaryotes. Here, we recapitulate several key functionalities ascribed to this known interacting protein pair by analysis of the placozoan proteins (Tap53 and TaMdm2) using both in vitro and cellular assays. In addition to interacting with each other, the Tap53 and TaMdm2 proteins are also able to respectively bind human Mdm2 and p53, providing strong evidence for functional conservation. The key p53-degrading function of Mdm2 is also conserved in TaMdm2. Tap53 retained DNA binding associated with p53 transcription activation function. However, it lacked transactivation function in reporter genes assays using a heterologous cell line, suggesting a cofactor incompatibility. Overall, the data supports functional roles for TaMdm2 and Tap53, and further defines the p53 pathway as an evolutionary conserved fulcrum mediating cellular response to stress.
p53Lab (A*STAR), 8A Biomedical Grove, #06-04/05 Neuros 138648, Singapore.
Jia Wei
JW
Siau
p53Lab (A*STAR), 8A Biomedical Grove, #06-04/05 Neuros 138648, Singapore.
Cynthia R
CR
Coffill
p53Lab (A*STAR), 8A Biomedical Grove, #06-04/05 Neuros 138648, Singapore.
Weiyun Villien
WV
Zhang
Bioinformatics Institute (A*STAR), 30 Biopolis Str, 07-01 Matrix 138671, Singapore.
Yaw Sing
YS
Tan
Technical University Munich, School of Life Sciences Weihenstephan, Alte Akademie 8, 85354 Freising, Germany.
Juliane
J
Hundt
p53Lab (A*STAR), 8A Biomedical Grove, #06-04/05 Neuros 138648, Singapore.
David
D
Lane
Bioinformatics Institute (A*STAR), 30 Biopolis Str, 07-01 Matrix 138671, Singapore.|School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive 637551, Singapore.|Department of Biological Sciences, National University of Singapore, 14 Science Drive 4 117543, Singapore.
Chandra
C
Verma
p53Lab (A*STAR), 8A Biomedical Grove, #06-04/05 Neuros 138648, Singapore.
Farid
F
Ghadessy
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