Related Experiment Video
Updated: Jun 12, 2026

12:02
Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols
Published on: June 6, 2017
Sequential counteracting kinases restrict an asymmetric gene expression program to early G1
1Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, IL 60208, USA.
Molecular Biology of the Cell
|June 25, 2010
Summary
Budding yeast Ace2 transcription factor activity is tightly controlled. Cyclin-dependent kinases (CDKs) inactivate Ace2, ensuring gene expression occurs only once per cell cycle.
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- Gene expression requires precise temporal control of transcription factors.
- In budding yeast, Ace2 transcription factor activity is restricted to daughter cells at the M-to-G1 transition.
- The kinase Cbk1 activates Ace2, but its inactivation mechanism remains unclear.
Purpose of the Study:
- To elucidate the mechanism of Ace2 transcription factor inactivation.
- To understand how Ace2 nuclear export and cytoplasmic sequestration are regulated.
- To identify the factors responsible for limiting Ace2 activity to a specific cell cycle phase.
Main Methods:
- Investigated Ace2 nuclear localization and phosphorylation in response to Cbk1 inhibition.
- Analyzed Ace2 interaction with G1 Cyclin-dependent kinases (CDKs) Pho85 and Cdc28.
- Utilized genetic and biochemical approaches to study Ace2 regulation.
Main Results:
- Ace2 nuclear localization depends on continuous Cbk1 activity; Cbk1 inhibition causes rapid dephosphorylation and cytoplasmic export.
- Ace2, once exported, cannot re-enter the nucleus for the rest of the cell cycle.
- Two redundant mechanisms ensure Ace2 cytoplasmic sequestration: phosphorylation by G1 CDKs and a Pho85-mediated, kinase-independent mechanism.
Conclusions:
- Sequential opposing kinases regulate Ace2 activity, restricting a daughter cell-specific transcriptional program to a narrow window.
- Cyclin-dependent kinases (CDKs) function as cytoplasmic sequestration factors for Ace2.
- This study reveals a novel mechanism for cell cycle-specific gene expression control.
Related Concept Videos
Inhibition of Cdk Activity
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Inhibition of CDK Activity
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Negative Regulator Molecules
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
The Cell Cycle Control System
The cell cycle regulation directs how a cell proceeds from one phase to the next and begins mitosis. The cell cycle control system includes intracellular regulatory molecules and external triggers. They provide "stop" or "advance" signals and operate at specific cell cycle stages termed checkpoints to ensure that a particular process is completed before the cell advances to the next phase.
Cyclins and cyclin-dependent kinases (Cdks) are the primary cell cycle regulators and function at the cell...
Cyclins and cyclin-dependent kinases (Cdks) are the primary cell cycle regulators and function at the cell...
The Cell Cycle Control System
The cell cycle is an organized set of events that leads the cell to divide into two daughter cells, each containing chromosomes identical to the parent cell. It is the cell cycle that leads to the formation of an entire organism from a single-cell zygote. Besides, cell division also functions in the renewal or repair of tissues in adult multicellular eukaryotes. For example, in the bone marrow, the stem cells divide to form new blood cells. Although essential for several functions, cell...
The Cell Cycle Control System
The cell cycle is an organized set of events that leads the cell to divide into two daughter cells, each containing chromosomes identical to the parent cell. It is the cell cycle that leads to the formation of an entire organism from a single-cell zygote. Besides, cell division also functions in the renewal or repair of tissues in adult multicellular eukaryotes. For example, in the bone marrow, the stem cells divide to form new blood cells. Although essential for several functions, cell...

