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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.
Inhibition of Cdk Activity02:34

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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...
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The Intrinsic Apoptotic Pathway01:31

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Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
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Related Experiment Video

Updated: May 9, 2026

Cell Death Associated with Abnormal Mitosis Observed by Confocal Imaging in Live Cancer Cells
15:53

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Published on: August 21, 2013

CIP2A inhibits PP2A in human malignancies.

Melissa R Junttila1, Pietri Puustinen, Minna Niemelä

  • 1Centre for Biotechnology, University of Turku and Abo Akademi University, 20520 Turku, Finland.

Cell
|July 17, 2007
PubMed
Summary

Cancerous Inhibitor of PP2A (CIP2A) is a newly identified oncoprotein that inhibits protein phosphatase 2A (PP2A) activity. CIP2A stabilizes the oncogenic transcription factor c-Myc, promoting human cancer development.

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Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Protein phosphatase 2A (PP2A) inhibition is crucial for human cell transformation.
  • The molecular mechanisms of PP2A inhibition in human cancers remain largely unknown.

Purpose of the Study:

  • To identify and characterize a cellular inhibitor of PP2A with oncogenic activity.
  • To elucidate the role of this inhibitor in human malignancies.

Main Methods:

  • Protein interaction studies to identify CIP2A.
  • Enzyme activity assays to measure PP2A inhibition.
  • Cellular assays for transformation and tumor formation.
  • Analysis of CIP2A expression in human cancers.

Main Results:

  • A novel protein, Cancerous Inhibitor of PP2A (CIP2A), was identified as a PP2A inhibitor.
  • CIP2A directly interacts with c-Myc, inhibiting PP2A activity at serine 62 (S62).
  • CIP2A prevents c-Myc degradation, promotes anchorage-independent growth, and induces tumor formation.
  • CIP2A is overexpressed in head and neck squamous cell carcinoma (HNSCC) and colon cancer.

Conclusions:

  • CIP2A is a human oncoprotein that inhibits PP2A and stabilizes c-Myc.
  • CIP2A plays a significant role in the development of human malignancies.