Related Experiment Video

Updated: Jul 5, 2026

Identification of MyoD Interactome Using Tandem Affinity Purification Coupled to Mass Spectrometry
14:47

Identification of MyoD Interactome Using Tandem Affinity Purification Coupled to Mass Spectrometry

Published on: May 17, 2016

Myostatin induces p300 degradation to silence cyclin D1 expression through the PI3K/PTEN/Akt pathway

Ming Ji1, Qiang Zhang, Jianwei Ye

  • 1National Laboratory of Medical Molecular Biology and Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Tsinghua University, 5 Dong Dan San Tiao, Beijing 100005, PR China.

Cellular Signalling
|May 13, 2008
PubMed

Insights

Myostatin silences cyclin D1 expression by degrading the p300 protein. This process involves the ubiquitin-proteasome system and is regulated by the PI3K/PTEN/Akt pathway, offering new insights into muscle growth control.

Area of Science:

  • Molecular Biology
  • Epigenetics
  • Skeletal Muscle Physiology

Background:

  • Myostatin negatively regulates skeletal muscle growth.
  • The precise mechanisms of myostatin-controlled gene expression are not fully understood.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which myostatin regulates gene expression.
  • To investigate the role of p300 and specific signaling pathways in myostatin's actions.

Main Methods:

  • Analysis of p300 recruitment to the cyclin D1 promoter.
  • Assessment of p300 protein levels and degradation pathways.
  • Investigation of the phosphatidylinositol 3-kinase/PTEN/Akt signaling pathway.

Main Results:

  • Myostatin inhibits cyclin D1 expression by preventing p300 recruitment to its promoter.
  • Myostatin induces p300 degradation through the ubiquitin-proteasome system.
  • Myostatin-induced p300 degradation is mediated by the PI3K/PTEN/Akt pathway, and can be counteracted by IGF-1 or insulin.

Conclusions:

  • Myostatin employs an epigenetic mechanism to control gene expression.
  • The findings reveal a novel pathway involving p300 degradation in myostatin signaling.
  • This study deepens the understanding of skeletal muscle growth regulation.

Related Concept Videos

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...
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...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
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...