Article
Biochemistry & Molecular Biology
M. Heider, Ruth Eichner, Jacob Stroh, Volker Morath, Anna Kuisl, Jana Zecha, Jannis Lawatscheck, Kheewoong Baek, Anne-Kathrin Garz, Martina Rudelius, Friedrich-Christian Deuschle, Ulrich Keller, Simone Lemeer, Mareike Verbeek, Katharina S. Gotze, Arne Skerra, Wolfgang A. Weber, Johannes Buchner, Brenda A. Schulman, Bernhard Kuster, Vanesa Fernandez-Saiz, Florian Bassermann
Summary: This study identifies the role of the CRBN-AHA1-HSP90 axis in the biogenesis of transmembrane proteins, linking IMiD activity to tumor metabolism, and nominating CD98hc and LAT1 as attractive diagnostic and therapeutic targets in MM.
Article
Medicine, General & Internal
Joanna Barankiewicz, Anna Szumera-Cieckiewicz, Aleksander Salomon-Perzynski, Paulina Wieszczy, Agata Malenda, Filip Garbicz, Monika Prochorec-Sobieszek, Irena Misiewicz-Krzeminska, Przemyslaw Juszczynski, Ewa Lech-Maranda
Summary: The study found that the expression of CRL4-CRBN complex proteins assessed by immunohistochemistry is associated with the treatment response and prognosis in multiple myeloma patients undergoing immunomodulatory drug therapy. This helps identify patients who are more likely to respond positively to immunomodulatory drug therapy.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Biotechnology & Applied Microbiology
Li Du, Wei Liu, Flavia Pichiorri, Steven T. Rosen
Summary: This study identified SUMOylation as a potential mechanism regulating lenalidomide resistance in multiple myeloma. Inhibition of SUMOylation can enhance sensitivity to lenalidomide by downregulating IRF4 expression.
CANCER GENE THERAPY
(2023)
Article
Biochemistry & Molecular Biology
Thayne Woycinck Kowalski, Marilea Furtado Feira, Vinicius Oliveira Lord, Julia do Amaral Gomes, Giovanna Camara Giudicelli, Lucas Rosa Fraga, Maria Teresa Vieira Sanseverino, Mariana Recamonde-Mendoza, Lavinia Schuler-Faccini, Fernanda Sales Luiz Vianna
Summary: This study aims to evaluate the transcription factors (TFs) altered by immunomodulatory drugs (IMiDs) through transcriptome and systems biology-allied analyses, with a focus on TFs associated with embryogenesis. Experimental data from bioinformatics databases were annotated for proteins and genes impacted by IMiDs, and a protein systems biology network was evaluated. CTNNB1 and SP1 were identified as key TFs in the network, with potential roles in IMiD-induced degradation. Additionally, a differential expression analysis of annotated genes from 23 transcriptomes identified 17 C2H2 TFs related to embryonic development as potential IMiDs degradation neosubstrates. This study presents the first evidence for an integration of IMiD molecular mechanisms through C2H2 TF degradation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Oncology
Lucia Y. Chen, Sarah Gooding
Summary: Resistance to immunomodulatory drugs (IMiDs) is a major cause of treatment failure in multiple myeloma (MM), and understanding the mechanisms behind this resistance is crucial for guiding treatment decisions. While the CRBN-dependent mechanisms of IMiD resistance are being discovered, additional mechanisms, including resistance within the immune microenvironment, need to be explored.
FRONTIERS IN ONCOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Arefeh Esmaeili, Mehdi Yoosefian, Mohamad Mahani
Summary: Lenalidomide, an immune-modulating drug, interacts with the CRBN protein to maintain cellular homeostasis and has shown promising therapeutic efficacy in treating haematological malignancies.
SOUTH AFRICAN JOURNAL OF CHEMISTRY-SUID-AFRIKAANSE TYDSKRIF VIR CHEMIE
(2023)
Article
Chemistry, Medicinal
Mikhail Krasavin, Maria Adamchik, Andrey Bubyrev, Christopher Heim, Samuel Maiwald, Daniil Zhukovsky, Petr Zhmurov, Alexander Bunev, Marcus D. Hartmann
Summary: In order to enhance the chemical toolkit for targeted protein degradation, the authors developed a new series of non-thalidomide Cereblon (CRBN) ligands. By using a thio-Michael addition reaction, readily available 2-methylidene glutarimide was converted to a series of 2-((hetero)aryl(methyl))thio glutarimides. These compounds were evaluated for their affinity to human CRBN and their binding modes were studied through X-ray crystallography. The newly identified Cereblon ligands show promising potential for the synthesis of novel PROTAC protein degraders.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Oncology
Mariko Ishibashi, Junichi Yamamoto, Takumi Ito, Hiroshi Handa, Mika Sunakawa-Kii, Koiti Inokuchi, Rimpei Morita, Hideto Tamura
Summary: IMiDs induce PD-L1 expression on MM cells through the BCMA-APRIL pathway and Ikaros degradation mediated by CRBN. Combination therapy of durvalumab and IMiDs effectively reverses T-cell inhibition induced by PD-L1-upregulated cells.
MOLECULAR CANCER THERAPEUTICS
(2021)
Review
Biology
Kazuhito Suzuki, Shingo Yano
Summary: This review discusses the strategies of IMiDs sequencing and IMiD-free interval for lenalidomide-refractory myeloma. It highlights the effectiveness of next-generation IMiDs such as pomalidomide and the potential of using PIs to restore cereblon and overcome lenalidomide resistance. The review also emphasizes the importance of considering safety profiles, social convenience, immunological environment, and genetic alterations in treatment selection.
Review
Oncology
Grzegorz Charlinski, David H. Vesole, Artur Jurczyszyn
Summary: Immunomodulatory drugs (IMiDs), due to their complex mechanism of actions, are a primary drug class used to treat multiple myeloma (MM). The standard of care currently involves combining IMiDs with corticosteroids and other drugs to improve outcomes in MM patients. Recent clinical trials have shown the effectiveness of newer cereblon inhibitors in MM treatment, even in cases refractory to approved IMiDs.
Article
Oncology
Angelina S. Bortoletto, Ronald J. Parchem
Summary: Extensive studies have shown that misregulation of individual miRNAs is associated with cancer. Recently, it has been discovered that mutations in the miRNA biogenesis and processing machinery are also involved in several malignancies. These mutations can cause global miRNA misregulation and contribute to cancer development. Additionally, it has been found that mutant KRAS can affect the activity of miRNA regulatory pathway members, further promoting tumorigenesis. Targeting both mutant KRAS and the miRNA core machinery may present a potential strategy for cancer treatment.
Article
Oncology
Matthew Ho, Saurabh Zanwar, Prashant Kapoor, Morie Gertz, Martha Lacy, Angela Dispenzieri, Suzanne Hayman, David Dingli, Francis Baudi, Eli Muchtar, Nelson Leung, Taxiarchis Kourelis, Rahma Warsame, Amie Fonder, Lisa Hwa, Miriam Hobbs, Robert Kyle, S. Vincent Rajkumar, Shaji Kumar
Summary: This study suggests that MM patients receiving >= 3 years of lenalidomide maintenance post-ASCT have superior outcomes. Lenalidomide refractoriness at first relapse is associated with inferior survival. At first relapse post-maintenance, daratumumab-based regimens show better survival outcomes.
BLOOD CANCER JOURNAL
(2021)
Article
Oncology
Nizar J. Bahlis, David S. Siegel, Gary J. Schiller, Christy Samaras, Michael Sebag, Jesus Berdeja, Siddhartha Ganguly, Jeffrey Matous, Kevin Song, Christopher S. Seet, Mirelis Acosta-Rivera, Michael Bar, Donald Quick, Bertrand Anz, Gustavo Fonseca, Weiyuan Chung, Kim Lee, Jorge Mouro, Amit Agarwal, Donna Reece
Summary: The combination therapy of pomalidomide, dexamethasone, and daratumumab shows good safety and efficacy in patients with relapsed/refractory multiple myeloma who have failed early-line lenalidomide treatment. This treatment regimen also demonstrates effectiveness in patients with lenalidomide-refractory disease.
LEUKEMIA & LYMPHOMA
(2022)
Article
Biochemical Research Methods
Rikke Kruse, James Krantz, Natalie Barker, Richard L. Coletta, Ruslan Rafikov, Moulun Luo, Kurt Hojlund, Lawrence J. Mandarino, Paul R. Langlais
MOLECULAR & CELLULAR PROTEOMICS
(2017)
Article
Biochemistry & Molecular Biology
Moulun Luo, Wayne T. Willis, Dawn K. Coletta, Paul R. Langlais, April Mengos, Wuqiong Ma, Jean Finlayson, Gregory R. Wagner, Chang-Xin Shi, Lawrence J. Mandarino
Article
Biochemistry & Molecular Biology
Moulun Luo, Wuqiong Ma, Zoe Sand, Jean Finlayson, Tian Wang, Roberta Diaz Brinton, Wayne T. Willis, Lawrence J. Mandarino
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2020)
Article
Multidisciplinary Sciences
Ritu Pandey, Muhan Zhou, Shariful Islam, Baowei Chen, Natalie K. Barker, Paul Langlais, Anup Srivastava, Moulun Luo, Laurence S. Cooke, Eric Weterings, Daruka Mahadevan
SCIENTIFIC REPORTS
(2019)
Review
Biochemistry & Molecular Biology
Riley J. Giesler, Patrick W. Erickson, Michael S. Kay
CURRENT OPINION IN CHEMICAL BIOLOGY
(2020)
Article
Hematology
Joel James, Marina Zemskova, Cody A. Eccles, Mathews V. Varghese, Maki Niihori, Natalie K. Barker, Moulun Luo, Lawrence J. Mandarino, Paul R. Langlais, Olga Rafikova, Ruslan Rafikov
Summary: The NFU1 mutation alters mitochondrial protein landscape, decreases respiratory function, enhances glycolysis and lipid metabolism, leading to a highly proliferative phenotype in pulmonary artery smooth muscle cells.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2021)
Article
Physiology
Rocio Zapata-Bustos, Jean Finlayson, Paul R. Langlais, Dawn K. Coletta, Moulun Luo, Danielle Grandjean, Elena A. De Filippis, Lawrence Mandarino
Summary: This study identified new candidate transcription factors that respond differently to exercise in insulin resistant individuals, compared to healthy individuals. The analysis of muscle proteome and transcription factors showed that abnormal responses to exercise may be responsible for differences in protein abundances in insulin resistant muscle.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Biochemical Research Methods
Jean Finlayson, Neusha Barakati, Paul R. Langlais, Janet Funk, Rocio Zapata Bustos, Dawn K. Coletta, Moulun Luo, Wayne T. Willis, Lawrence J. Mandarino
Summary: This study characterized ANT1 abundance and acetylation in human skeletal muscle using a novel method with small amounts of tissue samples. The findings indicate that acetylation of Lys23 reduces ADP binding to ANT1, providing insights into the potential effects of acetylation on ANT1 function in human muscle.
ANALYTICAL BIOCHEMISTRY
(2021)
Article
Biochemical Research Methods
Patrick W. Erickson, James M. Fulcher, Paul Spaltenstein, Michael S. Kay
Summary: Click-Assisted NCL (CAN) improves the slow ligation kinetics in protein total chemical synthesis by utilizing strain-promoted alkyne-azide cycloaddition (SPAAC) to accelerate ligations, protecting DBCO from acid-mediated rearrangement, and enhancing ligation efficiency. Initial experiments show promise for CAN in overcoming sterically hindered junctions in challenging ligations.
BIOCONJUGATE CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Paul M. Levine, Timothy W. Craven, Xinting Li, Aaron T. Balana, Gregory H. Bird, Marina Godes, Patrick J. Salveson, Patrick W. Erickson, Mila Lamb, Maggie Ahlrichs, Michael Murphy, Cassandra Ogohara, Meerit Y. Said, Loren D. Walensky, Matthew R. Pratt, David Baker
Summary: Peptide and protein bioconjugation technologies have revolutionized the ability to install functional groups at specific sites. This study introduces a site-specific bioconjugation strategy inspired by chemical ligation at serine, utilizing a noncanonical amino acid to create analogues of Semaglutide. The analogues show improved potency and stability, demonstrating the potential of serine ligation for generating stabilized peptide therapeutics.
ACS CHEMICAL BIOLOGY
(2022)
Article
Medicine, Research & Experimental
Neusha Barakati, Rocio Zapata Bustos, Dawn K. Coletta, Paul R. Langlais, Lindsay N. Kohler, Moulun Luo, Janet L. Funk, Wayne T. Willis, Lawrence J. Mandarino
Summary: The Delta RER method can reasonably estimate fuel oxidation in skeletal muscle activated by exercise. Resting skeletal muscle in insulin resistance prefers to oxidize carbohydrate rather than lipid, which may be related to low mitochondrial content.
METABOLIC SYNDROME AND RELATED DISORDERS
(2023)
Article
Biochemistry & Molecular Biology
Moulun Luo, Wuqiong Ma, Rocio Zapata-Bustos, Wayne T. Willis, Lawrence J. Mandarino
Summary: The deletion of VWA8 gene in hepatocytes resulted in higher mitochondrial and nonmitochondrial oxidative metabolism, despite sustained ROS production. The compensatory response in the mitochondria maintained overall higher oxidative capacity in VWA8 null cells.
BIOCHEMISTRY AND BIOPHYSICS REPORTS
(2021)
Review
Biochemistry & Molecular Biology
Michael T. Jacobsen, Patrick W. Erickson, Michael S. Kay
BIOORGANIC & MEDICINAL CHEMISTRY
(2017)
Article
Oncology
Yuan Xiao Zhu, Chang-Xin Shi, Laura A. Bruins, Patrick Jedlowski, Xuewei Wang, K. Martin Kortum, Moulun Luo, Jonathan M. Ahmann, Esteban Braggio, A. Keith Stewart
Article
Biochemistry & Molecular Biology
Moulun Luo, April E. Mengos, Wuqiong Ma, Jean Finlayson, Rocio Zapata Bustos, Yuan Xido Zhu, Chang-Xin Shi, Tianna M. Stubblefield, Wayne T. Willis, Lawrence J. Mandarino
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2017)