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Simultaneous expression of MMB-FOXM1 complex components enables efficient bypass of senescence
Ruchi Kumari1, Holger Hummerich1, Xu Shen2
1MRC Prion Unit at UCL, UCL Institute of Prion Diseases, 33 Cleveland Street, London, W1W 7FF, UK.
Scientific Reports
|November 3, 2021
Summary
Cellular senescence is a stable cell cycle arrest. The MMB-FOXM1 complex, containing LIN52, B-MYB, and FOXM1, bypasses senescence by disrupting the DREAM complex.
Area of Science:
- Cellular and Molecular Biology
- Cancer Biology
- Aging Research
Background:
- Cellular senescence is a critical tumor suppressor mechanism involving cell cycle arrest.
- The p53/p21 and pRB/p16 pathways are key in establishing senescence, but downstream effectors remain unclear.
- The DREAM complex (including MuvB core, p130, and E2F4) inhibits cell cycle genes to maintain arrest.
Purpose of the Study:
- To investigate the role of the DREAM complex and its components in maintaining cellular senescence.
- To identify downstream targets critical for the stability of the senescence growth arrest.
- To explore mechanisms for bypassing senescence using senescence-associated protein complexes.
Main Methods:
- Utilized a stable senescence bypass assay in conditionally immortalized human breast fibroblasts (CL3EcoR).
- Investigated the function of DREAM complex components, including LIN52, B-MYB, and FOXM1.
- Analyzed the role of LIN52 phosphorylation and DREAM complex assembly in senescence maintenance and bypass.
Main Results:
- Simultaneous expression of MMB-FOXM1 complex components (LIN52, B-MYB, FOXM1) efficiently bypasses senescence.
- Non-phosphorylated LIN52 is crucial for bypassing senescence, as it disrupts the DREAM complex.
- DREAM complex assembly is central to the maintenance of the senescence growth arrest.
Conclusions:
- The MMB-FOXM1 complex plays a critical role in overcoming cellular senescence.
- Disruption of the DREAM complex, facilitated by non-phosphorylated LIN52, is a key mechanism for senescence bypass.
- These findings highlight the importance of the DREAM complex in senescence stability and suggest potential therapeutic targets for age-related diseases and cancer.
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