Related Experiment Video

Updated: Jun 2, 2026

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
08:49

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries

Published on: January 22, 2019

CARD-mediated autoinhibition of cIAP1's E3 ligase activity suppresses cell proliferation and migration

Juanita Lopez1, Sidonie Wicky John, Tencho Tenev

  • 1Chester Beatty Laboratories, The Breakthrough Toby Robins Breast Cancer Research Centre, Institute of Cancer Research, Mary-Jean Mitchell Green Building, Fulham Road, London SW3 6JB, UK.

Molecular Cell
|May 10, 2011
PubMed

Insights

Cellular inhibitor of apoptosis 1 (cIAP1) autoregulation by its CARD domain suppresses E3 ligase activity, controlling cell proliferation, migration, and apoptosis.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Background:

  • E3 ligases regulate cellular processes through ubiquitylation.
  • Dysregulated ubiquitylation by E3 ligases, like cellular inhibitor of apoptosis (cIAP) proteins, is linked to diseases.
  • cIAP1 controls cell survival, proliferation, and migration.

Purpose of the Study:

  • To elucidate the regulatory mechanisms of cIAP1 E3 ligase activity.
  • To investigate the role of the caspase recruitment domain (CARD) of cIAP1 in its autoregulation.
  • To understand how cIAP1 autoregulation impacts biological processes and disease.

Main Methods:

  • Structural determination of the cIAP1 CARD domain.
  • Biochemical assays to assess E3 ligase activity, RING dimerization, and E2 binding/activation.
  • In vitro and in vivo experiments to evaluate effects on cell proliferation, migration, apoptosis, and vascular development.

Main Results:

  • The cIAP1 CARD domain directly inhibits E3 ligase activity by preventing RING dimerization and E2 complex formation/activation.
  • The CARD domain is essential for suppressing cell proliferation and migration.
  • CARD-mediated autoregulation is critical for suppressing caspase-8-dependent apoptosis and vascular tree degeneration in vivo.

Conclusions:

  • The cIAP1 CARD domain acts as an autoinhibitory module, controlling E3 ligase activity.
  • cIAP1 autoregulation is a key mechanism for maintaining cellular homeostasis.
  • Deregulation of cIAP1's E3 ligase activity by the CARD domain impacts cell proliferation, migration, and survival, with implications for disease.

More Related Videos

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

Knockdown of FAM83A to Verify Its Role in Cervical Cancer Cell Growth and Cisplatin Sensitivity04:20

Knockdown of FAM83A to Verify Its Role in Cervical Cancer Cell Growth and Cisplatin Sensitivity

Published on: February 9, 2024

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...
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...
Negative Regulator Molecules01:23

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.
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 daughter...
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...
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

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...