Related Experiment Video

Updated: Dec 8, 2025

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

6.5K

SHOC2 scaffold protein modulates daunorubicin-induced cell death through p53 modulation in lymphoid leukemia cells

Vanessa Silva Silveira1, Kleiton Silva Borges2, Verena Silva Santos3

  • 1Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil. vsilveira@fmrp.usp.br.

Scientific Reports
|September 17, 2020
PubMed

Insights

SHOC2 scaffold protein impacts leukemic cell drug response by modulating p53-induced cell death. Inhibiting SHOC2 impairs DNA damage response and apoptosis in pre-B acute lymphoid leukemia cells.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Biology

Background:

  • SHOC2 scaffold protein is linked to oncogenic ERK signaling via the RAS-SHOC2-PP1 complex.
  • SHOC2 upregulation correlates with improved survival in pediatric pre-B acute lymphoid leukemia, suggesting a prognostic role.
  • The paradoxical functions of SHOC2 in cancer require further investigation, particularly its impact on drug response.

Purpose of the Study:

  • To investigate the role of SHOC2 in modulating drug response in leukemic cells.
  • To elucidate the mechanism by which SHOC2 affects DNA-damage mediated apoptosis.
  • To determine if SHOC2 is essential for p53-induced cell death in pre-B lymphoid cells.

Main Methods:

  • Transcriptome analysis to assess SHOC2's impact on p53-mediated DNA damage.
  • Genetic inhibition of SHOC2 to evaluate effects on p53 expression and apoptosis.
  • Treatment with anti-leukemic drugs, including daunorubicin, to confirm SHOC2's role in DNA-damage induced cell death.

Main Results:

  • SHOC2 modulates p53-mediated DNA damage response.
  • Genetic inhibition of SHOC2 significantly impairs p53 expression, leading to blocked apoptosis.
  • SHOC2 is essential for cell death induction upon daunorubicin-induced DNA damage in human lymphoid cells.

Conclusions:

  • SHOC2 plays a critical role in activating p53-induced cell death in pre-B lymphoid cells.
  • SHOC2 is essential for the efficacy of certain anti-leukemic drugs by enabling DNA-damage response.
  • This study reveals a novel mechanism of SHOC2 function in regulating cell death pathways relevant to leukemia treatment.

More Related Videos

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

8.5K
Generation of Stable Human Cell Lines with Tetracycline-inducible Tet-on shRNA or cDNA Expression09:51

Generation of Stable Human Cell Lines with Tetracycline-inducible Tet-on shRNA or cDNA Expression

Published on: March 5, 2013

35.9K

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...
5.0K
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...
7.8K
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.
37.8K
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...
5.4K
Regulation of Hematopoietic Stem Cells01:01

Regulation of Hematopoietic Stem Cells

All blood and immune cells are produced from the multipotent hematopoietic stem cells (HSCs) by the process of hematopoiesis. However, they all have a limited life span. In addition, many are depleted in immune surveillance or combatting an injury or infection. This makes blood one of the most regenerative tissues. Hematopoiesis helps replenish these blood and immune cells, restoring the body's normal functioning. However, overproduction of blood and immune cells can make them cancerous or...
3.7K