FBXW8 regulates G1 and S phases of cell cycle progression by restricting ß-TrCP1 function.
FEBS J
; 288(18): 5474-5497, 2021 09.
Article
in En
| MEDLINE
| ID: mdl-33742524
Sequential alteration in the expression levels of cell cycle regulatory proteins is crucial for faithful cell cycle progression to maintain the cellular homeostasis. F-box protein ß-TrCP1 is known to control the expression levels of several important cell cycle regulatory proteins. However, how the function of ß-TrCP1 is regulated in spatiotemporal manner during cell cycle progression remains elusive. Here, we show that expression levels of ß-TrCP1 oscillate during cell cycle progression with a minimum level at the G1 and S phases of cell cycle. Using biochemical, flow cytometry, and immunofluorescence techniques, we found that oscillation of ß-TrCP1 expression is controlled by another F-box protein FBXW8. FBXW8 directs the proteasomal degradation of ß-TrCP1 in MAPK pathway-dependent manner. Interestingly, we found that the attenuation of ß-TrCP1 by FBXW8 is important for Cdc25A-mediated cell cycle transition from G1 phase to S phase as well as DNA damage-free progression of S phase. Overall, our study reveals the intriguing molecular mechanism and significance of maintenance of ß-TrCP1 levels during cell cycle progression by FBXW8-mediated proteasomal degradation.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cell Cycle Proteins
/
Cdc25 Phosphatases
/
F-Box Proteins
/
Beta-Transducin Repeat-Containing Proteins
Limits:
Humans
Language:
En
Journal:
FEBS J
Journal subject:
BIOQUIMICA
Year:
2021
Document type:
Article
Affiliation country:
India
Country of publication:
United kingdom