Cbl-c suppresses v-Src-induced transformation through ubiquitin-dependent protein degradation

Related Experiment Video

Updated: Aug 29, 2026

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs
10:44

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs

Published on: May 15, 2019

Minsoo Kim1, Tohru Tezuka, Keiji Tanaka

  • 1Division of Oncology, Department of Cancer Biology, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.

Oncogene
|December 9, 2003
PubMed

Insights

Cbl-c targets activated Src for degradation, reverting v-Src-induced cell transformation. This Cbl family member ubiquitinates Src, unlike Cbl and Cbl-b, suggesting distinct anti-cancer mechanisms.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Oncogenesis

Background:

  • Cbl family proteins (Cbl, Cbl-b, Cbl-c) regulate protein-tyrosine kinase signaling.
  • Their precise roles and targets in signaling pathways remain unclear.

Purpose of the Study:

  • To elucidate the specific signaling pathways and target proteins regulated by Cbl family members.
  • To investigate the role of Cbl-c in regulating Src signaling and v-Src-induced cell transformation.

Main Methods:

  • Investigated Cbl family protein function in v-Src-transformed NIH3T3 cells.
  • Analyzed v-Src protein levels and morphology changes.
  • Assessed protein ubiquitination and binding interactions using 293T cells and in vitro assays.

Main Results:

  • Cbl-c preferentially targets Src for degradation, reducing v-Src protein levels.
  • Cbl-c, but not Cbl or Cbl-b, reverted v-Src-induced cell morphology.
  • Cbl-c's TKB domain and RING finger are crucial for its anti-oncogenic activity.
  • Cbl-c directly ubiquitinates activated Src (phosphorylated at Tyr419) in vitro and in vivo.

Conclusions:

  • Activated Src is a direct target of Cbl-c, mediated by ubiquitination.
  • Cbl-c suppresses v-Src-induced transformation through a distinct mechanism involving Src degradation.
  • Cbl and Cbl-b likely employ different pathways to inhibit v-Src-induced transformation.

More Related Videos

Assaying Proteasomal Degradation in a Cell-free System in Plants07:43

Assaying Proteasomal Degradation in a Cell-free System in Plants

Published on: March 26, 2014

In-vitro Reconstitution of Bacterial Ubiquitination and VCP/p97-mediated Elimination07:58

In-vitro Reconstitution of Bacterial Ubiquitination and VCP/p97-mediated Elimination

Published on: January 2, 2026

Related Concept Videos

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...
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...
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 activation may...
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...
The Proteasome01:13

The Proteasome

Eukaryotic cells can degrade proteins through several pathways. One of the most important among these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3 (ubiquitin...
The Proteasome02:18

The Proteasome

Eukaryotic cells can degrade proteins through several pathways. One of the most important amongst these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...