C-terminal region of USP7/HAUSP is critical for deubiquitination activity and contains a second mdm2/p53 binding site

Ma, Jun; Martin, John D.; Xue, Yu; Lor, Leng A.; Kennedy-Wilson, Karen M.; Sinnamon, Robert H.; Ho, Thau; Zhang, Guofeng; Schwartz, Benjamin; Tummino, Peter J.; Lai, Zhihong

doi:10.1016/j.abb.2010.08.020

Cited by 58 publications

(65 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The USP7 UBL domains belong to the third group of the C-terminal UBLs. Previous studies revealed that UBLs of USP7 enhance its enzymatic activity, because even small truncations of the extreme C terminus dramatically decrease the USP7 catalytic activity (25,28). Furthermore, it was recently shown that the UBL domains can function as a binding platform for several USP7 substrates.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, it was recently shown that the UBL domains can function as a binding platform for several USP7 substrates. However, the precise location of the C-USP7 substrate-binding sites remained unknown (9,19,28).…”

Section: Discussionmentioning

confidence: 99%

“…The ICP0 E3 ligase from HSV-1 is the first USP7 substrate shown to interact exclusively with C-USP7, suggesting that the UBL domains may function as a platform for substrate binding. Recent studies revealed that the USP7 C-terminal region contains additional binding sites for p53 and Hdm2, as well as for the transcription factor FOX(O)4, which interacts exclusively with the C terminus (9,28). However, at this time no structural data are available for any of these C-USP7 complexes.…”

mentioning

confidence: 97%

See 2 more Smart Citations

Structural Characterization of Interaction between Human Ubiquitin-specific Protease 7 and Immediate-Early Protein ICP0 of Herpes Simplex Virus-1

Pozhidaeva

Mohni

Dhe‐Paganon

et al. 2015

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: Herpesvirus infection is dependent upon the viral E3 ligase ICP0 and its interaction with the human deubiquitinating enzyme USP7. Results: The interaction between USP7 and ICP0 was structurally characterized using solution NMR. Conclusion: ICP0 is recognized by ubiquitin-like domains 1 and 2 (UBL12) of the USP7. Significance: Details of the USP7/ICP0 interaction provide new insights into function of the USP7 ubiquitin-like domains.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 97%

See 1 more Smart Citation

Structural Characterization of Interaction between Human Ubiquitin-specific Protease 7 and Immediate-Early Protein ICP0 of Herpes Simplex Virus-1

Pozhidaeva

Mohni

Dhe‐Paganon

et al. 2015

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…4A). To verify the interaction between USP7 and MARCH7, we constructed a lowactivity USP7 truncation (pcDNA3.1-HA-tagged-USP7-1-1050) (Ma et al 2010) without changing its substratebinding affinity and over-expressed it in the SKOV3 cells. Immunoprecipitation results showed that both USP7-FL and USP7-1-1050 could pull-down MARCH7 (Fig.…”

Section: The Signaling Axis Of Usp7-march7-e-cadherin/β-cateninmentioning

confidence: 99%

“…The full length (FL, 1-1102) and low-activity truncation (1-1050) (Ma et al 2010) of human origin USP7 gene was constructed in the pcDNA3.1 vector (pcDNA3.1-USP7 and pcDNA3.1-USP7-1-1050), respectively. Cells were transfected with pcDNA3.1-plasmids (pcDNA3.1-vector, pcDNA3.1-USP7, pcDNA3.1-MARCH7) or siRNAs using Lipofectamine™ 2000 Transfection Reagent (Thermo Fisher Scientific, USA).…”

Section: Cell Culture and Transfectionmentioning

confidence: 99%

Expression of USP7 and MARCH7 Is Correlated with Poor Prognosis in Epithelial Ovarian Cancer

Zhang

Wang

Lin

et al. 2016

Tohoku J. Exp. Med.

View full text Add to dashboard Cite

Epithelial ovarian cancer (EOC) is one of the worst malignancies in females with poor overall survival due to the rapid metastasis and the absence of ideal biomarkers. Ubiquitin-specific protease 7 (USP7), an important deubiquitinating enzyme, was reported to be upregulated in several cancers, including liver, prostate and colon cancers. Membrane associated RING-CH protein 7 (MARCH7) belongs to the member of the E3 ubiquitin ligases. In addition, MARCH7 regulates T cell proliferation and the neuronal development and participates in the membrane trafficking and protein degradation. Importantly, MARCH7 itself is ubiquitinated and acts as a potential substrate of USP7. However, the roles of USP7 and MARCH7 in EOC remain to be investigated. We collected 121 EOC patients and analyzed the expression levels of USP7 and MARCH7 in tumor tissues with immunohistochemical staining. We found that the high expression of the two proteins was correlated with lymph node metastasis in EOC patients. Univariate and multivariate analyses revealed that the patients with high expression of the two proteins showed poorer prognosis compared with other patients. Subsequently, using SKOV3 human ovarian adenocarcinoma cells, we showed that either USP7 or MARCH7 enhanced the proliferation and invasion abilities. Moreover, USP7 could regulate the expression levels of E-cadherin and β-catenin through the MARCH7 signaling pathway. Our findings indicate that USP7 and MARCH7 are involved in the progression of EOC. In conclusion, analyzing the expression of USP7 and MARCH7 has high prognostic value in predicting EOC prognosis.

show abstract

MLF2 Negatively Regulates P53 and Promotes Colorectal Carcinogenesis

Fang

Zhao

et al. 2023

Advanced Science

View full text Add to dashboard Cite

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.

show abstract

C-terminal region of USP7/HAUSP is critical for deubiquitination activity and contains a second mdm2/p53 binding site

Cited by 58 publications

References 22 publications

Structural Characterization of Interaction between Human Ubiquitin-specific Protease 7 and Immediate-Early Protein ICP0 of Herpes Simplex Virus-1

Structural Characterization of Interaction between Human Ubiquitin-specific Protease 7 and Immediate-Early Protein ICP0 of Herpes Simplex Virus-1

Expression of USP7 and MARCH7 Is Correlated with Poor Prognosis in Epithelial Ovarian Cancer

MLF2 Negatively Regulates P53 and Promotes Colorectal Carcinogenesis

Contact Info

Product

Resources

About