Related Experiment Video

Updated: Aug 24, 2026

Promoter Capture Hi-C: High-resolution, Genome-wide Profiling of Promoter Interactions
10:16

Promoter Capture Hi-C: High-resolution, Genome-wide Profiling of Promoter Interactions

Published on: June 28, 2018

Pin1 links the activities of c-Abl and p300 in regulating p73 function

Fiamma Mantovani1, Silvano Piazza, Monica Gostissa

  • 1Laboratorio Nazionale C.I.B., Area Science Park, Padriciano 99, I-34012 Trieste, Italy.

Molecular Cell
|June 4, 2004
PubMed

Insights

The prolyl isomerase Pin1 is essential for tumor suppressor p73 stability and function. Pin1 facilitates p73

Area of Science:

  • Oncology
  • Molecular Biology
  • Cellular Biology

Background:

  • The tumor suppressor p73 plays a critical role in apoptosis induction in cancer cells lacking functional p53.
  • Genotoxic stress activates p73, involving kinases like c-Abl and acetyltransferases like p300.
  • The precise regulatory mechanisms governing p73 activation and stability remain incompletely understood.

Purpose of the Study:

  • To investigate the role of prolyl isomerase Pin1 in the regulation of p73 stability and function.
  • To elucidate the molecular interactions between Pin1, p73, c-Abl, and p300 during genotoxic stress.

Main Methods:

  • Utilized cell-based assays to assess p73 stability and transcriptional activity.
  • Investigated protein-protein interactions using co-immunoprecipitation assays.
  • Examined the effects of Pin1, c-Abl, and p300 on p73 phosphorylation, acetylation, and stability.

Main Results:

  • Pin1 catalyzes conformational changes in p73, which are crucial for its stability and accumulation upon genotoxic stress.
  • c-Abl enhances the phosphorylation-dependent interaction between Pin1 and p73 following chemotherapeutic drug treatment.
  • Pin1 is required for p73 acetylation by p300 and for the stabilizing and transcriptional activating effects of c-Abl and p300 on p73.

Conclusions:

  • Pin1 is essential for the activation of the apoptotic response mediated by endogenous p73.
  • The Pin1-p73 interaction is a critical regulatory step in the p53-independent apoptotic pathway.
  • Targeting the Pin1-p73 axis may represent a therapeutic strategy for cancers with defective p53.

More Related Videos

Co-immunoprecipitation Assay for Studying Functional Interactions Between Receptors and Enzymes09:40

Co-immunoprecipitation Assay for Studying Functional Interactions Between Receptors and Enzymes

Published on: September 28, 2018

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...
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...
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.
Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...