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Related Concept Videos

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...
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...
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...
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...
Intralumenal Vesicles and Multivesicular Bodies01:38

Intralumenal Vesicles and Multivesicular Bodies

Intraluminal vesicles (ILVs) are small vesicles 50-80 nm in diameter formed during the maturation of early endosomes. A specialized endosome containing numerous ILVs is called a multivesicular body (MVB). ILVs contain internalized molecules such as antigens, nucleic acids, proteins, and metabolites. Some of these molecules are released from the MVBs inside exosomes and are transported to other cells. Other MVBs contain molecules that are retained in the ILVs and are later degraded within the...
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...

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Related Experiment Video

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Comparative Strategies for Ubiquitination Detection in Mammalian Cell Lysates Using SMAD2/SMURF2 as a Model
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Comparative Strategies for Ubiquitination Detection in Mammalian Cell Lysates Using SMAD2/SMURF2 as a Model

Published on: April 17, 2026

Mcl-1 ubiquitination and destruction.

Hiroyuki Inuzuka1, Hidefumi Fukushima, Shavali Shaik

  • 1Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.

Oncotarget
|May 25, 2011
PubMed
Summary

Loss of Fbw7 tumor suppressor in T-cell acute lymphoblastic leukemia (T-ALL) leads to Mcl-1 overexpression, driving resistance to apoptosis. Targeting Mcl-1 offers a new therapeutic strategy for Fbw7-deficient T-ALL.

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Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Genetics

Background:

  • Loss of the Fbw7 tumor suppressor is frequent in human cancers, including T-cell acute lymphoblastic leukemia (T-ALL).
  • The precise anti-oncogenic mechanisms of Fbw7 are not fully understood.
  • SCFFbw7 controls Mcl-1 ubiquitination and degradation, impacting cellular apoptosis.

Purpose of the Study:

  • To elucidate the mechanistic basis of Fbw7's tumor suppressor function in T-ALL.
  • To investigate the relationship between Fbw7 loss, Mcl-1 expression, and drug sensitivity in T-ALL.
  • To identify potential therapeutic strategies for Fbw7-deficient T-ALL.

Main Methods:

  • Analysis of Fbw7 and Mcl-1 expression in human T-ALL cell lines.
  • Assessment of drug sensitivity to sorafenib and ABT-737 in Fbw7-deficient T-ALL cells.
  • Experimental manipulation of Fbw7 and Mcl-1 levels to study apoptosis regulation.

Main Results:

  • Fbw7-deficient T-ALL cell lines exhibit Mcl-1 overexpression.
  • These cells are sensitive to sorafenib but resistant to the Bcl-2 antagonist ABT-737.
  • Restoring Fbw7 or depleting Mcl-1 re-sensitizes cells to ABT-737, indicating Mcl-1's role in apoptosis evasion.

Conclusions:

  • Elevated Mcl-1 expression is crucial for Fbw7-deficient T-ALL cells to evade apoptosis.
  • This study reveals a novel mechanism for Fbw7 tumor suppression.
  • Targeting Mcl-1 with antagonists presents a promising therapeutic approach for Fbw7-deficient T-ALL patients.