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Anaphase Promoting Complex

Anaphase Promoting Complex

The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...

The Cell Cycle Control System

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...

Molecular Factors Affecting Cell Division

Molecular Factors Affecting Cell Division

Several external and internal factors influence the initiation and inhibition of cell division. For instance, the death of nearby cells or the release of human growth hormone (hGH) promotes cell division. In contrast, lack of hGH or crowding of cells can inhibit cell division.
Several proteins function as internal regulators to ensure each cell cycle stage is completed faithfully before proceeding to the next. Regulator molecules may act directly or influence the activity or production of other...

Separation of Sister Chromatids

Separation of Sister Chromatids

At the transition from prophase to metaphase, there is a reduction in cohesion along the chromosomal arms, resulting in the resolution of sister chromatids. However, residual cohesin connections remain to hold the sister chromatids together until the transition from metaphase to anaphase. The residual connection prevents any premature separation of sister chromatids, blocking the risks of aneuploidy within the daughter cells.
At the onset of anaphase, separase, a proteolytic enzyme, is...

Negative Regulator Molecules

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.

Positive Regulator Molecules

Positive Regulator Molecules

To consistently produce healthy cells, the cell cycle—the process that generates daughter cells—must be precisely regulated.

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Related Experiment Video

Updated: Aug 6, 2025

Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols

Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols

Published on: June 6, 2017

Lactate regulates cell cycle by remodelling the anaphase promoting complex.

Weihai Liu^1,2,3, Yun Wang^1,2,4, Luiz H M Bozi^1,2

¹Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.

|March 15, 2023

Summary

Accumulated lactate directly regulates cell division by inhibiting SENP1, which remodels the anaphase promoting complex (APC/C). This mechanism controls cell cycle progression and proliferation in rapidly dividing human cells.

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Last Updated: Aug 6, 2025

Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols

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Published on: June 6, 2017

Measuring Cell Cycle Progression Kinetics with Metabolic Labeling and Flow Cytometry

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Published on: May 22, 2012

Combining Mitotic Cell Synchronization and High Resolution Confocal Microscopy to Study the Role of Multifunctional Cell Cycle Proteins During Mitosis

Combining Mitotic Cell Synchronization and High Resolution Confocal Microscopy to Study the Role of Multifunctional Cell Cycle Proteins During Mitosis

Published on: December 5, 2017

Area of Science:

Biochemistry
Cell Biology
Cancer Research

Background:

Lactate is abundant in proliferating cells due to high glucose metabolism.
The role of accumulated lactate in regulating cell proliferation remains unclear.

Purpose of the Study:

To investigate lactate-dependent regulation of proteins in the human proteome.
To identify mechanisms by which lactate influences cell cycle progression.

Main Methods:

Systematic proteomic analysis to identify lactate-regulated proteins.
Biochemical assays to elucidate the interaction between lactate, SENP1, and APC/C.

Main Results:

Lactate accumulation remodels the anaphase promoting complex (APC/C) by inhibiting the SUMO protease SENP1.
Lactate binds zinc in the SENP1 active site, stabilizing SUMOylation of APC4 and driving UBE2C binding to APC/C.
This lactate-mediated APC/C regulation promotes timely degradation of cell cycle proteins and mitotic exit.

Conclusions:

Lactate directly regulates protein function to control the cell cycle and proliferation.
Aberrant lactate accumulation can lead to abnormal APC/C remodeling and mitotic slippage, potentially overcoming anti-mitotic drugs.