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The ASPP family: deciding between life and death after DNA damage
1Ludwig Institute for Cancer Research, Imperial College School of Medicine, St Mary's Campus, Norfolk Place, London W21PG, UK.
Abstract:
It is well established that p53 is a primary target for mutation in human cancer. p53 carries out the important task of ensuring that damaged DNA is not passed on during cell division, a duty that it performs by either inhibiting the cell cycle or inducing apoptosis. However, it is unclear how this decision is made. The recent identification of the ASPP family of proteins, which act to direct the cell away from cell cycle arrest and towards death following p53 upregulation, may explain how this dilemma is resolved. Furthermore, the observation that ASPP2 is in fact the full length form of the previously identified 53BP2/Bbp protein has clarified the ambiguous data that has been generated in relation to this molecule. The further characterisation of these proteins will enable us to gain further insights into the response of the cell to DNA damage and the progression of the cell towards malignancy.
Insights
The ASPP protein family may resolve the p53 dilemma, directing cells toward apoptosis rather than arrest after DNA damage. This clarifies the role of ASPP2 (53BP2/Bbp) in cancer progression and DNA damage response.
Area of Science:
- Molecular Biology
- Cell Biology
- Oncology
Background:
- The p53 protein is a critical tumor suppressor, frequently mutated in human cancers.
- p53 regulates cell fate decisions following DNA damage, including cell cycle arrest and apoptosis.
- The precise mechanisms governing p53's decision-making process remain incompletely understood.
Purpose of the Study:
- To investigate the role of the ASPP family of proteins in p53-mediated cellular responses.
- To elucidate how ASPP proteins influence the choice between cell cycle arrest and apoptosis.
- To clarify the identity and function of ASPP2, previously known as 53BP2/Bbp.
Main Methods:
- Identification and characterization of the ASPP protein family.
- Analysis of ASPP protein interactions with p53.
- Investigating the impact of ASPP proteins on cell cycle progression and apoptosis induction.
Main Results:
- The ASPP family directs p53-mediated responses towards apoptosis.
- ASPP2 is confirmed as the full-length form of 53BP2/Bbp, resolving previous data ambiguities.
- ASPP proteins play a key role in the cellular response to DNA damage.
Conclusions:
- ASPP proteins are crucial regulators of p53's tumor-suppressive functions.
- Understanding ASPP proteins offers insights into cancer development and DNA damage response.
- Targeting ASPP proteins may present novel therapeutic strategies for human cancers.