Molecular Cell: Deubiquitinases cleave ubiquitin-fused ribosomal proteins and physically counteract their targeting to the UFD pathway (Olsen)

December 1, 2025

Stephanie Patchett 1 5, Seyed Arad Moghadasi 1 5, Ankita Shukla 2, Farid El Oualid 3, Beatrix M. Ueberheide 1 4, Shaun K. Olsen 2, Tony T. Huang 1 6 Highlights Cleavage-resistant ubiquitin-fused human ribosomal proteins (RPs) impair ribosome function Unprocessed, Ub-fused RPs are targeted for proteasomal degradation by the UFD pathway DUB activity-based probes for Ub-fused RPs identify Cezanne/OTUD7B and other DUBs Catalytic activity-independent DUB association with Ub-RPs prevents their degradation Summary In eukaryotes, each ribosomal subunit includes [...]

Science Advances: Ligand-receptor interactions induce and mediate regulatory functions of BATF3+ B cells (Chen Lab, Zheng Lab)

November 12, 2025

Hui Yan  Rui Wang Suryavathi Viswanadhapalli  Christian Cervantes Funan He  Shuai Wu  Azad Khosh Weiwei Luo Jingwei Wang  Maria J. Fernandez Uday P. Pratap Mustafa Khan Karli Hinton  Sai Eashan Vankamamidi Dariela Perez Carlos E. Rivera Harshita B. Gupta  Fushun Zhang Zhenqing Ye Yidong Chen Xiao-Dong Li  Gangadhara R. Sareddy Hong Zan  Yue Li Exing Wang  Evelien M. Bunnik  Guangming Zhong Christopher A. Hunter  Ross M. Kedl Zhinan Yin  Booki Min Diako Ebrahimi  Siyuan Zheng  Tyler J. Curiel  Yan Xiang Ratna K. Vadlamudi , Paolo Casali  and Zhenming Xu [...]

ACS Medicinal Chemistry Letters: Identification and Exploration of a Series of SARS-Cov-2 MPro Cyano-Based Inhibitors Revealing Ortho-Substitution Effects within the P3 Biphenyl Group (Olsen)

November 10, 2025

Emma Clyde-Allen Mikołaj Zmudzinski Mohammad Afsar Ciyana James Anindita Nayak Digant Nayak Priscila dos Santos Bury Dirk Jochmans Johann Neyts Christopher J. Scott Shaun K. Olsen Marcin Drag Rich Williams* Abstract Starting from a simple scaffold hopping exercise based on our previous exploration of cysteine protease inhibitors against legumain, compound 6a was identified as a starting point [...]

Molecular Medicine: Selective inhibition of BRAF and CRAF sensitizes NF1-deficient malignant peripheral nerve sheath tumors to MEK inhibitors (Zheng, Kitagawa Lab)

October 2, 2025

      Jiawan Wang, Arnab Sarkar, Natalia Garcia, Lindy Zhang, Ana Calizo, Alla Lisok, Katia Campos, Funan He, Nishanth Punjaala, Teresa Marple, Kai Pollard, Siyuan Zheng, Calixto-Hope G. Lucas, Vesselina G. Cooke, Christine A. Pratilas & Angelina V. Vaseva Abstract Background Treatment for patients with malignant peripheral nerve sheath tumors (MPNST) is an unmet clinical [...]

Nature Structural & Molecular Biology: Cryo-EM structures reveal the molecular mechanism of SUMO E1–E2 thioester transfer (Olsen Lab, Sung Lab)

September 26, 2025

Anindita Nayak, Digant Nayak, Lijia Jia, Eliza A. Ruben, Suryavathi Viswanadhapalli, Priscila dos Santos Bury, Khaled Mohamed Nassar, Corey H. Yu, Anna A. Tumanova, Caleb M. Stratton, Pirouz Ebadi, Dmitri N. Ivanov, Patrick Sung, Ratna K. Vadlamudi, Elizabeth V. Wasmuth & Shaun K. Olsen Abstract Post-translational modification of proteins by SUMO (small ubiquitin-like modifier) regulates fundamental [...]

BioRxiv: Phosphoregulation of RAD51AP1 function in homology-directed repair (Sung Lab)

September 22, 2025

Neelam Sharma, Mollie Uhrig, Youngho Kwon, Patrick Sung,  Claudia Wiese ABSTRACT Homology-directed DNA repair (HDR) is critical for genome stability and tumor suppression. HDR is initiated by the RAD51 single-stranded (ss)DNA nucleoprotein filament which conducts the homology search and invades a homologous DNA template, creating a displacement-loop (D-loop). The RAD51 filament is assisted in these processes by several proteins. One [...]

Protein Science: Molecular basis of EWS interdomain self-association and its role in condensate formation (Libich Lab)

September 22, 2025

Erich J. Sohn, Kandarp A. Sojitra, Leticia Rodrigues, Xiaoping Xu, Bess Frost, Jeetain Mittal, David S. Libich Abstract Ewing sarcoma, the second most common pediatric bone and soft tissue cancer, is caused by the aberrant fusion of the RNA-binding protein EWS (EWS) low-complexity domain (EWSLCD) to the DNA-binding domain of the transcription factor friend leukemia integration 1 (FLI1). The resulting fusion, [...]

Trends in Biochemical Sciences: E3 Ubiquitin Ligases in Signaling, Disease, and Therapeutics (Olsen)

September 15, 2025

Pirouz Ebadi 1, Caleb M Stratton 1, Shaun K Olsen 2 Abstract The ubiquitin-proteasome system (UPS) is a central regulator of protein turnover and signaling, with E3 ubiquitin ligases conferring substrate specificity and chain-type control. Recent advances have revealed new mechanistic classes of E3 ligases and expanded our understanding of their roles in disease, including cancer, neurodegeneration, and immune dysfunction. [...]

Aging Cell: Inhibition of Hippo Signaling Through Ablation of Lats1 and Lats2 Protects Against Cognitive Decline in 5xFAD Mice via Increasing Neuronal Resilience Against Ferroptosis (Zheng)

September 10, 2025

Robert C. Evans, Nawab John Dar, Liuji Chen, Ren Na, Jason C. O'Connor, Jing Jiang, Siyuan Zheng, Qitao Ran ABSTRACT The Hippo signaling pathway is a key regulator of cell growth and cell survival, and hyperactivation of the Hippo pathway has been implicated in neurodegenerative diseases such as Huntington's disease. However, the role of Hippo signaling in Alzheimer's disease (AD) remains unclear. [...]

Expert Opinion on Therapeutic Targets: Rhabdomyosarcoma: development of molecular therapeutics under the microscope (Houghton)

August 15, 2025

Peter J. Houghton Mary-Ann Bjornsti ABSTRACT Rhabdomyosarcoma (RMS), predominantly diagnosed in children, represents 3% of the pediatric solid tumors. RMS has characteristics of skeletal muscle, although the cell of origin remains controversial. Cytotoxic therapeutics, radiation treatment, and surgery remain the standard of care; however, outcomes for advanced disease have not changed for several decades. Major [...]