MLF2 Negatively Regulates P53 and Promotes Colorectal Carcinogenesis
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Updated: Jul 23, 2025

Deficient Pms2, ERCC1, Ku86, CcOI in Field Defects During Progression to Colon Cancer
Published on: July 28, 2010
Debao Fang1,2, Hao Hu2, Kailiang Zhao1,2
1Department of Thoracic Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, China.
Abstract:
Inactivation of the p53 pathway is linked to a variety of human cancers. As a critical component of the p53 pathway, ubiquitin-specific protease 7 (USP7) acts as a deubiquitinase for both p53 and its ubiquitin E3 ligase mouse double minute 2 homolog. Here, myeloid leukemia factor 2 (MLF2) is reported as a new negative regulator of p53. MLF2 interacts with both p53 and USP7. Via these interactions, MLF2 inhibits the binding of USP7 to p53 and antagonizes USP7-mediated deubiquitination of p53, thereby leading to p53 destabilization. Functionally, MLF2 plays an oncogenic role in colorectal cancer, at least partially, via the negative regulation of p53. Clinically, MLF2 is elevated in colorectal cancer and its high expression is associated with poor prognosis in patients with colorectal cancer. In wild-type-p53-containing colorectal cancer, MLF2 and p53 expressions are inversely correlated. These findings establish MLF2 as an important suppressor of p53 function. The study also reveals a critical role for the MLF2-p53 axis in promoting colorectal carcinogenesis.
Insights
Myeloid leukemia factor 2 (MLF2) negatively regulates the p53 pathway by inhibiting USP7 binding to p53, promoting colorectal cancer. MLF2 is elevated in colorectal cancer and linked to poor prognosis.
Area of Science:
- Molecular Biology
- Oncology
- Biochemistry
Background:
- The p53 pathway is crucial for preventing cancer, and its inactivation is common in human malignancies.
- Ubiquitin-specific protease 7 (USP7) is a key regulator of p53 stability through deubiquitination.
Purpose of the Study:
- To identify novel regulators of the p53 pathway.
- To investigate the role of myeloid leukemia factor 2 (MLF2) in p53 regulation and colorectal cancer.
Main Methods:
- Co-immunoprecipitation assays to study protein interactions.
- Western blotting to assess protein levels and stability.
- Analysis of patient data to correlate MLF2 expression with colorectal cancer prognosis.
Main Results:
- Myeloid leukemia factor 2 (MLF2) was identified as a novel negative regulator of p53.
- MLF2 directly interacts with p53 and USP7, inhibiting USP7-mediated p53 deubiquitination and promoting p53 destabilization.
- MLF2 expression is elevated in colorectal cancer tissues and associated with poor patient prognosis.
- MLF2 plays an oncogenic role in colorectal cancer, partly through p53 suppression.
Conclusions:
- MLF2 acts as a critical suppressor of p53 function.
- The MLF2-p53 axis is implicated in the development and progression of colorectal cancer.
- MLF2 represents a potential therapeutic target in colorectal cancer.
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