Related Experiment Video

Updated: Jun 21, 2026

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter
11:32

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter

Published on: March 27, 2020

Autoregulatory control of the p53 response by Siah-1L-mediated HIPK2 degradation

Marco A Calzado1, Laureano de la Vega, Eduardo Muñoz

  • 1Departmento de Biología Celular, Fisiología e Immunología, Facultad de Medicina, Universidad de Córdoba, Avda. Menéndez Pidal, s/n, E-14004 Córdoba, Spain.

Biological Chemistry
|August 1, 2009
PubMed

Insights

The tumor suppressor p53 is regulated by feedback loops. Siah-1L ligase targets HIPK2 and HIPK3 kinases, creating a negative feedback loop that controls p53 activity.

Area of Science:

  • Molecular biology
  • Cellular signaling
  • Cancer research

Background:

  • The tumor suppressor p53 is crucial for cellular responses to stress.
  • p53 activity is tightly regulated by complex feedback mechanisms.
  • Understanding these regulatory loops is vital for cancer therapy.

Purpose of the Study:

  • To investigate the role of Siah-1L in regulating p53 activity.
  • To identify novel interactions and feedback mechanisms involving p53.
  • To elucidate the function of HIPK family kinases in p53 signaling.

Main Methods:

  • Co-immunoprecipitation assays to detect protein interactions.
  • Ubiquitination assays to assess protein modification.
  • Proteasomal degradation assays to measure protein stability.
  • Reporter gene assays to quantify p53-triggered transcription.

Main Results:

  • Siah-1L directly binds to HIPK2 and promotes its ubiquitination and proteasomal degradation.
  • Siah-1L also targets HIPK3 for degradation, indicating broader activity within the HIPK family.
  • Siah-1L antagonizes the stimulatory effect of HIPK2 on p53-mediated transcription.

Conclusions:

  • Siah-1L acts as a negative regulator of p53 activity by targeting HIPK2 and HIPK3.
  • This interaction represents a novel negative feedback loop controlling the p53 response.
  • The findings provide new insights into the intricate regulation of tumor suppressor p53.

More Related Videos

Assessing Cellular Target Engagement by SHP2 (PTPN11) Phosphatase Inhibitors08:45

Assessing Cellular Target Engagement by SHP2 (PTPN11) Phosphatase Inhibitors

Published on: July 17, 2020

Yeast As a Chassis for Developing Functional Assays to Study Human P5314:57

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

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 daughter...
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.
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...
DNA Damage can Stall the Cell Cycle02:36

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...
DNA Damage Can Stall the Cell Cycle02:36

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...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...