Related Experiment Video

Updated: Mar 15, 2026

Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors
08:45

Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors

Published on: July 17, 2020

6.7K

MST2 phosphorylation at serine 385 in mitosis inhibits its tumor suppressing activity

Xingcheng Chen1, Yuanhong Chen2, Jixin Dong2

  • 1Eppley Institute for Research in Cancer, Fred & Pamela Buffett Cancer Center, United States; Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, United States.

Cellular Signalling
|August 28, 2016
PubMed

Insights

Mammalian sterile 20-like kinase 2 (MST2), a tumor suppressor, is regulated by cyclin-dependent kinase 1 (CDK1) phosphorylation during mitosis. This regulation impacts its role in suppressing cancer cell proliferation and tumorigenesis.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Oncology

Background:

  • Mammalian sterile 20-like kinase 1/2 (MST1/2) are key tumor suppressors within the Hippo signaling pathway.
  • MST1/2 play a crucial role in regulating mitotic progression.

Purpose of the Study:

  • To elucidate a novel mechanism of MST2 phosphorylation during mitosis.
  • To investigate the biological significance of MST2 mitotic phosphorylation in cancer development.

Main Methods:

  • In vitro and in vivo kinase assays to identify MST2 phosphorylation sites.
  • Analysis of MST2 phosphorylation during unperturbed and drug-induced mitosis.
  • Assessment of cell proliferation, anchorage-independent growth, and tumorigenesis using wild-type and phosphorylation-deficient MST2 mutants.

Main Results:

  • Cyclin-dependent kinase 1 (CDK1) phosphorylates MST2 at serine 385 during mitosis.
  • This phosphorylation is transient during normal mitosis and occurs during G2/M arrest induced by antimitotic drugs.
  • Mitotic phosphorylation of MST2 does not alter its kinase activity or Hippo-YAP signaling.
  • The MST2-S385A mutant, deficient in mitotic phosphorylation, exhibits enhanced suppression of cell proliferation, anchorage-independent growth, and in vivo tumorigenesis.

Conclusions:

  • A novel regulatory mechanism for MST2 phosphorylation in mitosis has been identified.
  • Mitotic phosphorylation of MST2 plays a critical role in regulating its tumor-suppressive functions.
  • Targeting MST2 phosphorylation may offer new therapeutic strategies for cancer treatment.
Keywords:
CDK1MST2Mitotic phosphorylationTumor suppressor

More Related Videos

Combining Mitotic Cell Synchronization and High Resolution Confocal Microscopy to Study the Role of Multifunctional Cell Cycle Proteins During Mitosis08:33

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

15.1K
Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics06:00

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics

Published on: May 14, 2016

11.6K

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.4K
Inhibition of Cdk Activity02:34

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...
6.1K
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
6.2K
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

2.0K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
5.0K
DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
10.3K