Related Experiment Video

Updated: May 30, 2025

In Vivo Detection and Analysis of Rb Protein SUMOylation in Human Cells
09:40

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

Published on: November 2, 2017

7.2K

Smurf2 Suppresses Proliferation and Cell Cycle of Triple-Negative Breast Cancer Cells by Promoting the

Siyu Wei1,2,3, Yuying Liu1,2,3, Zhihao Wang1,2,3

  • 1Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.

Journal of Cellular and Molecular Medicine
|January 28, 2025
PubMed

Insights

SMAD-specific E3 ubiquitin protein ligase 2 (Smurf2) suppresses triple-negative breast cancer (TNBC) cell proliferation by targeting human L35a ribosomal protein (RPL35A) for degradation. This mechanism inhibits the G1/S phase transition, impacting TNBC progression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Human L35a ribosomal protein (RPL35A) is implicated in drug resistance and viability in triple-negative breast cancer (TNBC).
  • The precise mechanism by which RPL35A promotes TNBC malignant progression remains largely undefined.
  • Understanding these mechanisms is crucial for developing targeted therapies for TNBC.

Purpose of the Study:

  • To elucidate the mechanism underlying RPL35A's role in TNBC progression.
  • To identify upstream regulators of RPL35A involved in TNBC cell proliferation.
  • To investigate the therapeutic potential of targeting the RPL35A pathway in TNBC.

Main Methods:

  • Gene silencing techniques were used to assess the impact of RPL35A on TNBC cell proliferation.
  • Co-immunoprecipitation assays were employed to investigate the interaction between Smurf2 and RPL35A.
  • Western blotting and ubiquitination assays were performed to analyze RPL35A degradation and polyubiquitination.
  • Xenograft mouse models were utilized to validate the in vivo efficacy of Smurf2.
  • Analysis of human TNBC tissues was conducted to correlate RPL35A and Smurf2 protein levels.

Main Results:

  • Silencing RPL35A inhibited TNBC cell proliferation by suppressing the G1/S phase transition.
  • SMAD-specific E3 ubiquitin protein ligase 2 (Smurf2) was identified as an upstream ubiquitin ligase of RPL35A.
  • Smurf2 interacted with RPL35A, promoting its degradation and K63-linked polyubiquitination, thereby inhibiting cell cycle progression.
  • Smurf2 demonstrated inhibitory effects on TNBC growth in a xenograft mouse model.
  • A negative correlation was observed between RPL35A and Smurf2 protein levels in human TNBC tissues.

Conclusions:

  • Smurf2 acts as a tumor suppressor in TNBC by inhibiting cell proliferation.
  • Smurf2 regulates RPL35A stability and ubiquitination, leading to cell cycle arrest at the G1/S phase.
  • The Smurf2-RPL35A axis represents a potential therapeutic target for managing TNBC progression.
Keywords:
L35a ribosomal proteinSMAD‐specific E3 ubiquitin protein ligase 2proliferation and cell cycletriple‐negative breast cancerubiquitination

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

2.1K
Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

12.8K

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...
4.4K
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.
35.1K
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...
3.7K
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR...
2.0K
Regulated Protein Degradation02:58

Regulated Protein Degradation

It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
7.1K
Positive Regulator Molecules01:45

Positive Regulator Molecules

To consistently produce healthy cells, the cell cycle—the process that generates daughter cells—must be precisely regulated.
105.7K