Related Experiment Video

Updated: Feb 22, 2026

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants
07:38

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Published on: June 6, 2025

839

The Cks1/Cks2 axis fine-tunes Mll1 expression and is crucial for MLL-rearranged leukaemia cell viability

William Grey1, Adam Ivey1, Thomas A Milne2

  • 1Department of Medical and Molecular Genetics, King's College London, Faculty of Life Sciences and Medicine, London, UK.

Biochimica Et Biophysica Acta. Molecular Cell Research
|September 24, 2017
PubMed

Insights

Cks1 and Cks2 proteins regulate MLL1 levels, impacting cell cycle and cancer. Inhibiting Cks1/2 reduced proliferation in MLL-rearranged leukemia cell lines, suggesting a new therapeutic target.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • Cdc28-associated proteins Cks1 and Cks2 regulate cyclin-dependent kinase (Cdk) substrate specificity and protein degradation.
  • These proteins interact with E3 ubiquitin ligase complexes SCFSkp2 and APCCdc20, targeting proteins like p27 and Cyclin A.
  • Overexpression of CKS1B and CKS2 is linked to various human cancers, including MLL-rearranged (MLLr) acute myeloid leukemia (AML).

Purpose of the Study:

  • To investigate the interaction between Cks1/Cks2 and Mixed-lineage leukemia 1 (MLL1) protein.
  • To determine the role of Cks1 and Cks2 in regulating MLL1 levels throughout the cell cycle.
  • To explore the therapeutic potential of targeting Cks1/Cks2 in MLLr leukemia.

Main Methods:

  • Co-immunoprecipitation assays to confirm Cks1/Cks2 interaction with MLL1 subunits (MllN and MllC).
  • Cell cycle analysis to assess MLL1 level regulation by Cks proteins.
  • Treatment of MLLr cell lines with small molecule inhibitors (MLN4924 and C1) targeting protein degradation pathways.

Main Results:

  • Cks1 and Cks2 directly interact with both MllN and MllC subunits of MLL1.
  • Cks proteins are crucial for defining MLL1 protein levels across the cell cycle.
  • Inhibition of Cks1/Cks2-mediated protein degradation significantly reduced proliferation in MLLr cell lines compared to controls.

Conclusions:

  • Cks1 and Cks2 establish a novel regulatory pathway for MLL1.
  • This Cks-MLL1 interaction presents a potential therapeutic strategy for MLLr leukemia.
  • Targeting Cks proteins may offer a new avenue for treating MLLr leukemias.
Keywords:
CKS1BCKS2MLL-fusion proteinsMLL1SKP2/CKS1 inhibitorWnt

More Related Videos

Proliferation and Differentiation of Murine Myeloid Precursor 32D/G-CSF-R Cells10:21

Proliferation and Differentiation of Murine Myeloid Precursor 32D/G-CSF-R Cells

Published on: February 21, 2018

10.5K
Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence10:09

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence

Published on: January 7, 2019

8.8K

Related Concept Videos

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...
6.7K
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
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...
5.3K
Positive Regulator Molecules02:39

Positive Regulator Molecules

Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
7.0K
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
8.2K
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...
3.5K