Related Experiment Video

Updated: Aug 10, 2025

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay
12:26

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay

Published on: May 3, 2018

18.7K

Phosphorylation of USP29 by CDK1 Governs TWIST1 Stability and Oncogenic Functions

Tangming Guan1, Mei Li1, Yan Song2

  • 1College of Pharmacy/International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education (MOE) of China, Jinan University, Guangzhou, 510632, China.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|February 14, 2023
PubMed

Insights

USP29 stabilizes TWIST1 in triple-negative breast cancer (TNBC), promoting chemo-resistance and metastasis. Targeting the CDK1-USP29 axis offers a new therapeutic strategy for TNBC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Triple-negative breast cancer (TNBC) is aggressive with limited treatment options.
  • TWIST1, a transcription factor, drives epithelial-mesenchymal transition (EMT), cancer stem cell (CSC) properties, and metastasis in TNBC.
  • The precise mechanisms regulating TWIST1 in TNBC are not fully understood.

Purpose of the Study:

  • To identify regulators of TWIST1 in TNBC.
  • To elucidate the role of USP29 and CDK1 in TNBC pathogenesis.
  • To explore the therapeutic potential of targeting the CDK1-USP29 axis.

Main Methods:

  • Biochemical assays to identify USP29 as a TWIST1 deubiquitinase.
  • Cellular experiments to assess the impact of USP29 and CDK1 on EMT and CSC phenotypes.
  • In vivo studies and histological analysis of TNBC patient samples.
  • Genetic and pharmacological inhibition of CDK1.

Main Results:

  • USP29 deubiquitinates and stabilizes TWIST1, promoting EMT and CSC functions in TNBC.
  • CDK1 directly activates USP29 through phosphorylation, enhancing its deubiquitinase activity towards TWIST1.
  • Inhibition of CDK1 significantly reduces TWIST1-driven malignant phenotypes.
  • CDK1 and USP29 are upregulated in TNBC tissues and correlate with TWIST1 expression.

Conclusions:

  • The CDK1-USP29 axis stabilizes TWIST1, driving TNBC progression, chemo-resistance, and metastasis.
  • Targeting the CDK1-USP29 axis represents a promising therapeutic strategy for TNBC.
  • This study uncovers a novel tumor-promoting mechanism and clinical significance of the CDK1-USP29 pathway in TNBC.
Keywords:
CDK1TWIST1USP29chemotherapeutic resistancemetastasis

More Related Videos

Purification of Ubiquitinated p53 Proteins from Mammalian Cells10:55

Purification of Ubiquitinated p53 Proteins from Mammalian Cells

Published on: March 21, 2022

2.2K
In Vivo Detection and Analysis of Rb Protein SUMOylation in Human Cells09:40

In Vivo Detection and Analysis of Rb Protein SUMOylation in Human Cells

Published on: November 2, 2017

7.4K

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...
4.9K
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...
2.9K
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....
6.9K
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...
3.8K
DNA Damage can Stall the Cell Cycle02:37

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...
9.2K
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...
3.8K