Dmp53 activates the Hippo pathway to promote cell death in response to DNA damage

TY - JOUR

T1 - Dmp53 activates the Hippo pathway to promote cell death in response to DNA damage

AU - Colombani, Julien

AU - Polesello, Cédric

AU - Josué, Filipe

AU - Tapon, Nicolas

PY - 2006/7/25

Y1 - 2006/7/25

N2 - Developmental and environmental signals control a precise program of growth, proliferation, and cell death. This program ensures that animals reach, but do not exceed, their typical size . Understanding how cells sense the limits of tissue size and respond accordingly by exiting the cell cycle or undergoing apoptosis has important implications for both developmental and cancer biology. The Hippo (Hpo) pathway comprises the kinases Hpo and Warts/Lats (Wts), the adaptors Salvador (Sav) and Mob1 as a tumor suppressor (Mats), the cytoskeletal proteins Expanded and Merlin, and the transcriptional cofactor Yorkie (Yki) . This pathway has been shown to restrict cell division and promote apoptosis. The caspase repressor DIAP1 appears to be a primary target of the Hpo pathway in cell-death control. Firstly, Hpo promotes DIAP1 phosphorylation, likely decreasing its stability. Secondly, Wts phosphorylates and inactivates Yki, decreasing DIAP1 transcription. Although we understand some of the events downstream of the Hpo kinase, its mode of activation remains mysterious. Here, we show that Hpo can be activated by Ionizing Radiations (IR) in a Dmp53 (Drosophila melanogaster p53)-dependent manner and that Hpo is required (though not absolutely) for the cell death response elicited by IR or Dmp53 ectopic expression.

AB - Developmental and environmental signals control a precise program of growth, proliferation, and cell death. This program ensures that animals reach, but do not exceed, their typical size . Understanding how cells sense the limits of tissue size and respond accordingly by exiting the cell cycle or undergoing apoptosis has important implications for both developmental and cancer biology. The Hippo (Hpo) pathway comprises the kinases Hpo and Warts/Lats (Wts), the adaptors Salvador (Sav) and Mob1 as a tumor suppressor (Mats), the cytoskeletal proteins Expanded and Merlin, and the transcriptional cofactor Yorkie (Yki) . This pathway has been shown to restrict cell division and promote apoptosis. The caspase repressor DIAP1 appears to be a primary target of the Hpo pathway in cell-death control. Firstly, Hpo promotes DIAP1 phosphorylation, likely decreasing its stability. Secondly, Wts phosphorylates and inactivates Yki, decreasing DIAP1 transcription. Although we understand some of the events downstream of the Hpo kinase, its mode of activation remains mysterious. Here, we show that Hpo can be activated by Ionizing Radiations (IR) in a Dmp53 (Drosophila melanogaster p53)-dependent manner and that Hpo is required (though not absolutely) for the cell death response elicited by IR or Dmp53 ectopic expression.

KW - Animals

KW - Apoptosis/physiology

KW - Caspases/analysis

KW - Cell Cycle Proteins/genetics

KW - DNA Damage

KW - Drosophila Proteins/genetics

KW - Drosophila melanogaster/cytology

KW - Gamma Rays

KW - Gene Expression Regulation, Developmental

KW - Green Fluorescent Proteins/analysis

KW - Intracellular Signaling Peptides and Proteins

KW - Larva/cytology

KW - Mutation

KW - Protein Kinases/genetics

KW - Protein-Serine-Threonine Kinases/metabolism

KW - Signal Transduction/radiation effects

KW - Tumor Suppressor Protein p53/genetics

U2 - 10.1016/j.cub.2006.05.059

DO - 10.1016/j.cub.2006.05.059

M3 - Journal article

C2 - 16860746

SN - 0960-9822

VL - 16

SP - 1453

EP - 1458

JO - Current Biology

JF - Current Biology

IS - 14

ER -