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Human cyclin F
C Bai1, R Richman, S J Elledge
1Howard Hughes Medical Institute, Verna and Marrs McLean Department of Biochemistry, Baylor College of Medicine, Houston, TX 77030.
Abstract:
Cyclins are important regulators of cell cycle transitions through their ability to bind and activate cyclin-dependent protein kinases. In mammals several classes of cyclins exist which are thought to co-ordinate the timing of different events necessary for cell cycle progression. Here we describe the identification of a novel human cyclin, cyclin F, isolated as a suppressor of the G1/S deficiency of a Saccharomyces cerevisiae cdc4 mutant. Cyclin F is the largest cyclin, with a molecular weight of 87 kDa, and migrates as a 100-110 kDa protein. It contains an extensive PEST-rich C-terminus and a cyclin box region that is most closely related to cyclins A and B. Cyclin F mRNA is ubiquitiously expressed in human tissues. It fluctuates dramatically through the cell cycle, peaking in G2 like cyclin A and decreasing prior to decline of cyclin B mRNA. Cyclin F protein accumulates in interphase and is destroyed at mitosis at a time distinct from cyclin B. Cyclin F shows regulated subcellular localization, being localized in the nucleus in most cells, with a significant percentage of cells displaying only perinuclear staining. Overexpression of cyclin F, or a mutant lacking the PEST region, in human cells resulted in a significant increase in the G2 population, implicating cyclin F in the regulation of cell cycle transitions. The ubiquitous expression and phylogentic conservation of cyclin F suggests that it is likely to coordinate essential cell cycle events distinct from those regulated by other cyclins.
Insights
Researchers discovered a new human protein, cyclin F, crucial for cell cycle regulation. This protein plays a key role in coordinating cell division events, distinct from other known cyclins.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- Cyclins are key regulators of cell cycle transitions by activating cyclin-dependent protein kinases.
- Mammalian cells utilize various cyclins to coordinate cell cycle progression.
- The precise roles of all cyclins in cell cycle control are not fully elucidated.
Purpose of the Study:
- To identify and characterize a novel human cyclin, designated cyclin F.
- To investigate the function of cyclin F in cell cycle regulation.
- To understand the expression pattern and localization of cyclin F.
Main Methods:
- Isolation of human cyclin F as a suppressor of a yeast cell cycle mutant (cdc4).
- Analysis of cyclin F molecular weight, protein domains (PEST-rich C-terminus, cyclin box), and mRNA expression.
- Investigation of cyclin F protein accumulation, degradation timing, and subcellular localization (nucleus, perinuclear).
- Functional studies involving overexpression of cyclin F and a mutant lacking the PEST region in human cells.
Main Results:
- Cyclin F is the largest known cyclin (87 kDa), with a PEST-rich C-terminus and a cyclin box similar to cyclins A and B.
- Cyclin F mRNA is ubiquitously expressed and its levels fluctuate during the cell cycle, peaking in G2.
- Cyclin F protein accumulates during interphase and is degraded at mitosis, with distinct subcellular localization.
- Overexpression of cyclin F leads to an increased G2 cell population.
Conclusions:
- Cyclin F is a novel, ubiquitously expressed human cyclin involved in cell cycle regulation.
- Its unique expression, localization, and cell cycle-dependent degradation suggest a distinct role from other cyclins.
- Cyclin F likely coordinates essential cell cycle events, contributing to the overall control of cell division.