Wenyi Wei

Beth Israel Deaconess Medical Center

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Trends

Author Order

Document Type

Co-Authors

Hiroyuki Inuzuka

Beth Israel Deaconess Medical Center

120

Lixin Wan

Molecular Oncology (United States)

Pengda Liu

University of North Carolina at Chapel Hill

Jianping Guo

Sun Yat-sen University

Daming Gao

Chinese Academy of Sciences

Jinfang Zhang

Wuhan University

Jing Liu

Shanghai Stomatological Hospital

Zhiwei Wang

Bengbu Medical College

Wenjian Gan

Medical University of South Carolina

Xiangpeng Dai

First Hospital of Jilin University

Cooperative Institutions

Harvard University

416

Beth Israel Deaconess Medical Center

197

Chinese Academy of Sciences

164

Brigham and Women's Hospital

120

Shanghai Jiao Tong University

115

Dana-Farber Cancer Institute

107

University of Chinese Academy of Sciences

103

Sun Yat-sen University

101

Chinese Academy of Medical Sciences & Peking Union Medical College

Wuhan University

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Field

Role of SKP1-CUL1-F-Box-Protein (SCF) E3 Ubiquitin Ligases in Skin Cancer

Journal of genetics and genomics/Journal of Genetics and Genomics (2013)

Chuan-Ming Xie Wenyi Wei Yi Sun

Skp1

F-box protein

Ubiquitin-Protein Ligases

Protein Degradation

DDB1

Ubiquitin-conjugating enzyme

10.1016/j.jgg.2013.02.001

Cite

Citations (40)

USP7-Based Deubiquitinase-Targeting Chimeras Stabilize AMPK

Journal of the American Chemical Society (2024)

Jing Liu Xiaoping Hu Kaixiu Luo Yan Xiong Li Chen

Deubiquitinase-targeting chimeras (DUBTACs) have been recently developed to stabilize proteins of interest, which is in contrast to targeted protein degradation (TPD) approaches that degrade disease-causing proteins. However, to date, only the OTUB1 deubiquitinase has been utilized to develop DUBTACs via an OTUB1 covalent ligand, which could unexpectedly compromise the endogenous function of OTUB1 owing to its covalent nature. Here, we show for the first time that deubiquitinase USP7 can be harnessed for DUBTAC development. Based on a noncovalent ligand of USP7, we developed USP7-based DUBTACs that stabilized the ΔF508-CFTR mutant protein as effectively as the previously reported OTUB1-based DUBTAC. Importantly, using two different noncovalent ligands of USP7, we developed the first AMPK DUBTACs that appear to selectively stabilize different isoforms of AMPKβ, leading to elevated AMPK signaling. Overall, these results highlight that, in addition to OTUB1, USP7 can be leveraged to develop DUBTACs, thus significantly expanding the limited toolbox for targeted protein stabilization and the development of novel AMPK DUBTACs as potential therapeutics.

Deubiquitinating enzyme

Conjugate

10.1021/jacs.4c02373

Cite

Citations (4)

ubiquitylation-mediated proteolysis of PAX3 to suppress melanocyte proliferation and melanoma growth

Juxiang Cao Xiangpeng Dai Lixin Wan Hongshen Wang Jinfang Zhang

Proteolysis

Melanocyte

Source

Cite

Citations (0)

Table S1 from FBW7 Loss Promotes Chromosomal Instability and Tumorigenesis via Cyclin E1/CDK2–Mediated Phosphorylation of CENP-A

Mamoru Takada Weiguo Zhang Aussie Suzuki Taruho S. Kuroda Zhouliang Yu

<p>Table S1: Antibodies used in this paper.</p>

Chromosome instability

Cyclin E

10.1158/0008-5472.22414268.v1

Cite

Citations (0)

Hippo signaling is intrinsically regulated during cell cycle progression by APC/C ^Cdh1

Proceedings of the National Academy of Sciences (2019)

Wantae Kim Yong Suk Cho Xiaohui Wang Ogyi Park Xueyan Ma

The Hippo-YAP/TAZ signaling pathway plays a pivotal role in growth control during development and regeneration and its dysregulation is widely implicated in various cancers. To further understand the cellular and molecular mechanisms underlying Hippo signaling regulation, we have found that activities of core Hippo signaling components, large tumor suppressor (LATS) kinases and YAP/TAZ transcription factors, oscillate during mitotic cell cycle. We further identified that the anaphase-promoting complex/cyclosome (APC/C) Cdh1 E3 ubiquitin ligase complex, which plays a key role governing eukaryotic cell cycle progression, intrinsically regulates Hippo signaling activities. CDH1 recognizes LATS kinases to promote their degradation and, hence, YAP/TAZ regulation by LATS phosphorylation is under cell cycle control. As a result, YAP/TAZ activities peak in G1 phase. Furthermore, we show in Drosophila eye and wing development that Cdh1 is required in vivo to regulate the LATS homolog Warts with a conserved mechanism. Cdh1 reduction increased Warts levels, which resulted in reduction of the eye and wing sizes in a Yorkie dependent manner. Therefore, LATS degradation by APC/C Cdh1 represents a previously unappreciated and evolutionarily conserved layer of Hippo signaling regulation.

Hippo signaling pathway

CDH1

E2F

Anaphase-promoting complex

10.1073/pnas.1821370116

Cite

Citations (55)

PROTAC technology for the treatment of Alzheimer’s disease: advances and perspectives

Acta Materia Medica (2022)

Hiroyuki Inuzuka Jing Liu Wenyi Wei Abdol-Hossein Rezaeian

Neurodegenerative diseases (NDs) are characteristic with progression of neuron degeneration, resulting in dysfunction of cognition and mobility. Many neurodegenerative diseases are because of proteinopathies that results from unusual protein accumulations and aggregations. The aggregation of misfolded proteins like β-amyloid, α-synuclein, tau, and polyglutamates are hallmarked in Alzheimer's disease (AD), which are undruggable targets, and usually do not respond to conventional small-molecule agents. Therefore, developing novel technology and strategy for reducing the levels of protein aggregates would be critical for treatment of AD. Recently, the emerging proteolysis targeting chimeras (PRPTACs) technology has been significantly considered for artificial and selective degradation of aberrant target proteins. These engineered bifunctional molecules engage target proteins to be degraded by either the cellular degradation machinery in the ubiquitin-proteasome system (UPS) or via the autophagy-lysosome degradation pathway. Although the application of PROTACs technology is preferable than oligonucleotide and antibodies for treatment of NDs, many limitations such as their pharmacokinetic properties, tissue distribution and cell permeabilities, still need to be corrected. Herein, we review the recent advances in PROTACs technology with their limitation for pharmaceutical targeting of aberrant proteins involved in Alzheimer's diseases. We also review therapeutic potential of dysregulated signaling such as PI3K/AKT/mTOR axis for the management of AD.

Protein Degradation

Amyloid (mycology)

10.15212/amm-2021-0001

Cite

Citations (35)

Targeting tumor micro-environmental pathways for cancer therapy

Seminars in Cancer Biology (2023)

Qing Zhang Wenyi Wei

Cancer Therapy

10.1016/j.semcancer.2023.01.009

Cite

Citations (1)

Telomere Targeting Chimera Enables Targeted Destruction of Telomeric Repeat-Binding Factor Proteins

Journal of the American Chemical Society (2023)

Zhen Wang Jing Liu He Chen Xing Qiu Ling Xie

Telomeres are naturally shortened after each round of cell division in noncancerous normal cells, while the activation of telomerase activity to extend telomere in the cancer cell is essential for cell transformation. Therefore, telomeres are regarded as a potential anticancer target. In this study, we report the development of a nucleotide-based proteolysis-targeting chimera (PROTAC) designed to degrade TRF1/2 (telomeric repeat-binding factor 1/2), which are the key components of the shelterin complex (telosome) that regulates the telomere length by directly interacting with telomere DNA repeats. The prototype telomere-targeting chimeras (TeloTACs) efficiently degrade TRF1/2 in a VHL- and proteosome-dependent manner, resulting in the shortening of telomeres and suppressed cancer cell proliferation. Compared to the traditional receptor-based off-target therapy, TeloTACs have potential application in a broad spectrum of cancer cell lines due to their ability to selectively kill cancer cells that overexpress TRF1/2. In summary, TeloTACs provide a nucleotide-based degradation approach for shortening the telomere and inhibiting tumor cell growth, representing a promising avenue for cancer treatment.

Shelterin

Chimera (genetics)

10.1021/jacs.3c02783

Cite

Citations (16)

Loss of retinoblastoma but not p16 function allows bypass of replicative senescence in human fibroblasts

EMBO Reports (2003)

Wenyi Wei Utz Herbig Shan Wei Annie Dutriaux John M. Sedivy

Senescence

Retinoblastoma protein

Retinoblastoma

10.1038/sj.embor.7400001