ASPP2 Is Phosphorylated by CDK1 during Mitosis and Required for Pancreatic Cancer Cell Proliferation

Yi Xiao1, Yuanhong Chen1, Jianan Chen1

  • 1Eppley Institute for Research in Cancer and Allied Diseases, Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, USA.

Cancers
|November 25, 2023
PubMed

Insights

Apoptosis-stimulating protein of p53-2 (ASPP2) is phosphorylated during mitosis by CDK1. ASPP2 is crucial for pancreatic cancer growth and may be a therapeutic target.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Biology

Background:

  • Pancreatic cancer is a lethal disease with unclear molecular mechanisms.
  • The role of apoptosis-stimulating protein of p53-2 (ASPP2) in pancreatic cancer is largely unknown.
  • Previous work identified cell cycle-dependent alterations in ASPP family proteins.

Purpose of the Study:

  • To elucidate the phosphorylation regulation of ASPP2 during mitosis.
  • To investigate the functional role of ASPP2 in pancreatic cancer progression.
  • To identify downstream targets of ASPP2 in pancreatic cancer.

Main Methods:

  • Phosphate-binding tag (Phos-tag) SDS-PAGE to analyze ASPP2 phosphorylation.
  • Generation of phospho-specific antibodies for validation.
  • ASPP2-inducible expression cell lines and RNA sequencing (RNA-Seq) for functional studies.

Main Results:

  • ASPP2 is phosphorylated by cyclin-dependent kinase 1 (CDK1) at serine residues S562 and S704 during mitosis.
  • ASPP2 is essential for pancreatic cancer cell growth in vitro and in vivo.
  • Depletion of ASPP2 significantly alters the expression of YAP-related genes.

Conclusions:

  • ASPP2 phosphorylation by CDK1 is a key regulatory mechanism during mitosis.
  • ASPP2 plays a critical role in promoting pancreatic cancer growth.
  • ASPP2 represents a potential therapeutic target for pancreatic cancer treatment.

Related Concept Videos

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...
4.8K
Anaphase Promoting Complex00:50

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...
2.9K
Separation of Sister Chromatids02:17

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...
3.7K
M-Cdk Drives Transition Into Mitosis02:15

M-Cdk Drives Transition Into Mitosis

Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
5.6K
DNA Damage can Stall the Cell Cycle02:37

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...
9.2K
The Spindle Assembly Checkpoint02:19

The Spindle Assembly Checkpoint

The spindle assembly checkpoint is a molecular surveillance mechanism ensuring the fidelity of chromosome segregation during anaphase. The checkpoint monitors the completion of all the prerequisite steps before chromosome segregation to determine whether the segregation process should proceed or be delayed.
Many proteins function together to control the spindle assembly checkpoint. Mutations affecting these proteins may allow cells to proceed into anaphase prematurely, resulting in the...
3.2K