Article
Pharmacology & Pharmacy
Xianlong Gao, Garrett A. Enten, Michelle Y. McGee, McWayne Weche, Matthias Majetschak
Summary: We previously reported that alpha(1)-adrenoceptor (alpha(1)-AR) ligands can inhibit chemokine receptor (CR) heteromerization partners of alpha(1B/D)-AR. In this study, we investigated the mechanisms underlying this inhibition and provided in vivo evidence using a murine air pouch model. Our findings demonstrate that alpha(1B)-AR enhances G(alpha i) signaling of CCR2, and phenylephrine and phentolamine can reduce the heteromerization propensity and inhibit G(ai) signaling of CCR2. Additionally, phenylephrine was found to recruit beta-arrestin-2 to CCR2 and decrease the expression of alpha(1B/D)-AR, CR partners, and corresponding heteromers, while phentolamine specifically reduced CR: alpha(1B/D)-AR heteromers without affecting beta-arrestin-2 recruitment or receptor expression. Overall, our study provides new insights into the pharmacology of GPCR heteromers and highlights the potential therapeutic significance of targeting alpha(1B)-AR:CR heteromerization.
PHARMACOLOGICAL RESEARCH
(2023)
Article
Neurosciences
Jiapei Huang, Lan Yi, Xiaoxiao Yang, Qi Zheng, Jun Zhong, Sen Ye, Xican Li, Hui Li, Dongfeng Chen, Caixia Li
Summary: The transplantation of NSCs combined with ethyl stearate can improve the motor behavioral performance of PD rats by promoting NSCs migration and differentiation into dopaminergic neurons through CCL5/CCR5 signaling pathway.
CNS NEUROSCIENCE & THERAPEUTICS
(2023)
Article
Medicine, Research & Experimental
Xiaoqian Shang, Liang Wang, Yumei Liu, Xuemei Liu, Jie Lv, Xuan Zhou, Hao Wang, Shaxika Nazierhan, Jing Wang, Xiumin Ma
Summary: The study investigated the role of CXCR3 and its ligands in diagnosing spinal tuberculosis (ST), finding that IFN-gamma, CXCR3, and CXCL10 were significantly elevated in ST patients, serving as more reliable diagnostic markers.
EXPERIMENTAL AND THERAPEUTIC MEDICINE
(2021)
Review
Oncology
Xianxian Wu, Hongdian Zhang, Zhilin Sui, Yang Wang, Zhentao Yu
Summary: Esophageal squamous cell carcinoma is the main type of esophageal cancer, where abnormal expression of CXCL12 and CXCR4 contributes to tumor proliferation, distant metastases, and worsening prognosis. Antagonists and imaging agents targeting CXCL12/CXCR4 have been developed to interfere with and monitor tumor metastasis.
CANCER BIOLOGY & MEDICINE
(2021)
Article
Radiology, Nuclear Medicine & Medical Imaging
Andreas K. Buck, Goetz Ulrich Grigoleit, Sabrina Kraus, Andreas Schirbel, Michael Heinsch, Niklas Dreher, Takahiro Higuchi, Constantin Lapa, Heribert Haenscheid, Samuel Samnick, Hermann Einsele, Sebastian E. Serfling, Rudolf A. Werner
Summary: In this study, we investigated the use of CXCR4-targeted radioligand therapy (RLT) as a conditioning regimen for hematopoietic stem cell transplantation (HSCT) in patients with advanced T-cell lymphoma. The results showed that CXCR4-directed RLT can be an effective treatment option, leading to remarkable antilymphoma activity in selected cases.
JOURNAL OF NUCLEAR MEDICINE
(2023)
Article
Radiology, Nuclear Medicine & Medical Imaging
Andreas K. Buck, Alexander Haug, Niklas Dreher, Alessandro Lambertini, Takahiro Higuchi, Constantin Lapa, Alexander Weich, Martin G. Pomper, Hans-Juergen Wester, Anja Zehndner, Andreas Schirbel, Samuel Samnick, Marcus Hacker, Verena Pichler, Stefanie Hahner, Martin Fassnacht, Hermann Einsele, Sebastian E. Serfling, Rudolf A. Werner
Summary: In recent years, molecular imaging targeting CXCR4 has been increasingly used in various clinical settings. This study aimed to assess radiopharmaceutical uptake and image contrast to determine the clinical applications for CXCR4-directed imaging and investigate the impact of specific activity on scan contrast.
JOURNAL OF NUCLEAR MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Xiaoyu Zheng, Xige Zhao, Yijia Wang, Jing Chen, Xiaotong Wang, Xia Peng, Li Ma, Juan Du
Summary: During embryonic development, the proliferation, migration, osteogenesis, and epithelial-mesenchymal transition of embryonic palatal mesenchymal cells play crucial roles in palate development. This study found that knockdown of the Cxcr4 gene inhibits cell migration, and supplementation with CXCL12 partially reverses this inhibition. The combination of low-dose retinoic acid and plerixafor increases the incidence of cleft palate by affecting the expression of Cxcr4 and its downstream genes involved in cell migration.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Medicine, Research & Experimental
Weibo Feng, Wenjie Huang, Jie Chen, Chenyang Qiao, Danfei Liu, Xiaoyu Ji, Meng Xie, Tongyue Zhang, Yijun Wang, Mengyu Sung, Dean Tian, Daiming Fan, Yongzhan Nie, Kaichun Wu, Limin Xia
Summary: HOXB5 gene plays a crucial role in promoting colorectal cancer metastasis by transactivating metastatic related genes CXCR4 and ITGB3. Additionally, a positive feedback loop of CXCL12-HOXB5-CXCR4 has been identified to have an important role in colorectal cancer metastasis.
Review
Medicine, General & Internal
He-Yun Sun, Zhi-Chao Min, Lei Gao, Zi-Yi Zhang, Ting-Le Pang, Ying-Jun Gao, Hong Pan, Jun Ou-Yang
Summary: IL8RB C1208T mutation may be associated with the risk of various cancers, especially prostate adenocarcinoma.
Review
Cell Biology
Dianne M. Perez
Summary: Alpha(1)-adrenergic receptors play various roles in the body beyond regulating vascular smooth muscle contraction and blood pressure, including neurotransmission, cognition, and cardiac protection. Advances in research using transgenic and knockout mouse models, as well as more selective ligands, have provided deeper insights into their physiological functions.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Pharmacology & Pharmacy
Weiwei Yu, Ting Ye, Jie Ding, Yi Huang, Yang Peng, Qin Xia, Zhang Cuntai
Summary: The study found that the expression of CCL3 is increased in COPD, causing damage to TJs through CCR5, while miR-4456 can suppress the effect of CCL3 on TJs by binding to the 3'-UTR of CCL3, suggesting that the miR-4456/CCL3/CCR5 pathway could be a potential target for COPD treatment.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Radiology, Nuclear Medicine & Medical Imaging
Andreas K. Buck, Sebastian E. Serfling, Sabrina Kraus, Samuel Samnick, Niklas Dreher, Takahiro Higuchi, Leo Rasche, Hermann Einsele, Rudolf A. Werner
Summary: This article discusses the novel and established radiopharmaceuticals used for treating hematologic neoplasms, the use of small molecules specifically binding to C-X-C motif chemokine receptor 4 as theranostic agents, and the advantages and disadvantages of lymphoma treatment using radioimmunoconjugates.
JOURNAL OF NUCLEAR MEDICINE
(2023)
Article
Immunology
Serena Melgrati, Oliver J. Gerken, Marc Artinger, Egle Radice, Martyna Szpakowska, Andy Chevigne, Giulia D'Uonnolo, Paola Antonello, Sylvia Thelen, Pawel Pelczar, Daniel F. Legler, Marcus Thelen
Summary: Immune responses rely on immune cell trafficking in secondary lymphoid organs. Atypical chemokine receptors (ACKRs) scavenge chemokines to guide leukocytes. GPR182, a potential novel ACKR, acts as a scavenging receptor for chemokines and does not activate typical intracellular signaling. Cooperation between GPR182 and other ACKRs affects chemokine levels and influences immune responses.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Gastroenterology & Hepatology
Qinbo Cai, Peng Shi, Yujie Yuan, Jianjun Peng, Xinde Ou, Wen Zhou, Jin Li, Taiqiang Su, Liangliang Lin, Shirong Cai, Yulong He, Jianbo Xu
Summary: The study revealed a new mechanism of H pylori-induced atrophic gastritis through CXCR2-mediated cellular senescence. Inhibition of CXCR2 signaling is suggested as a potential preventive therapy for targeting H pylori-induced atrophic gastritis.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2021)
Article
Pharmacology & Pharmacy
Yuanyuan Deng, Ruirong Tan, Fei Li, Yuangui Liu, Jingshan Shi, Qihai Gong
Summary: The study found that IRN treatment can reduce infarct volume, improve neurological function, decrease neuronal death rate, brain water content, and aquaporin-4 expression in the ischemic penumbra of I/R injury rats' brains. In addition, IRN treatment can inhibit I kappa B-alpha degradation, NF-kappa B p65 activation, CX3CR1 expression, as well as microglial activation and inflammatory response. These findings suggest that IRN is a promising candidate for treating cerebral I/R injury by inhibiting microglial activation and neuroinflammation.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Michael J. Wedemeyer, Sarah A. Mahn, Anthony E. Getschman, Kyler S. Crawford, Francis C. Peterson, Adriano Marchese, John D. McCorvy, Brian F. Volkman
JOURNAL OF BIOLOGICAL CHEMISTRY
(2020)
Article
Multidisciplinary Sciences
Favin S. Babu, Xiaomei Liang, Garrett A. Enten, Anthony J. DeSantis, Brian F. Volkman, Xianlong Gao, Matthias Majetschak
SCIENTIFIC REPORTS
(2020)
Article
Biochemistry & Molecular Biology
Acacia F. Dishman, Francis C. Peterson, Brian F. Volkman
Summary: XCL1 is a metamorphic protein that switches between two distinct native structures with different functions in the human immune system. Recent studies show that an engineered XCL1 variant called CC5 can regulate XCL1's structural equilibrium, resulting in an enrichment of the antimicrobial structure.
Article
Multidisciplinary Sciences
Acacia F. Dishman, Robert C. Tyler, Jamie C. Fox, Andrew B. Kleist, Kenneth E. Prehoda, M. Madan Babu, Francis C. Peterson, Brian F. Volkman
Summary: Through ancestral reconstruction and nuclear magnetic resonance, this study investigated the evolution of the metamorphic protein XCL1 and how it switches between two distinct folds. The evolution of XCL1 involved changes in dimer interface, structural constraints, and intramolecular protein contacts, leading to the development of its two different folds. These findings offer insights into how one sequence can evolve to encode multiple structures, with implications for protein design and engineering.
Article
Oncology
Deepak Parashar, Anjali Geethadevi, Donna McAllister, Johnathan Ebben, Francis C. Peterson, Davin R. Jensen, Erin Bishop, Sunila Pradeep, Brian F. Volkman, Michael B. Dwinell, Pradeep Chaluvally-Raghavan, Michael A. James
Summary: Recurrence of therapy-resistant tumors remains a major challenge in the field of solid tumor oncology, particularly in ovarian and pancreatic cancer. High expression of CLPTM1L in ovarian tumor cells is associated with poor prognosis, and inhibiting CLPTM1L can re-sensitize resistant ovarian cancer cells to platinum-based therapy. Additionally, CLPTM1L can confer intercellular resistance to chemotherapeutic killing in an ectodomain-dependent manner, which can be blocked by anti-CLPTM1L biologics.
NPJ PRECISION ONCOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Lara Rheinemann, Tuscan Thompson, Gaelle Mercenne, Elliott L. Paine, Francis C. Peterson, Brian F. Volkman, Steven L. Alam, Akram Alian, Wesley Sundquist
Summary: HIV, like many enveloped viruses, requires host cell machinery for assembly and budding through plasma membrane. Proteins like AMOT and NEDD4L promote virion membrane envelopment and release, with specific interaction between AMOT PPxY1 motif and NEDD4L WW3 domain critical for HIV-1 infectivity.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Timothy J. Stodola, Young-In Chi, Thiago M. De Assuncao, Elise N. Leverence, Swarnendu Tripathi, Nikita R. Dsouza, Angela J. Mathison, Brian Volkman, Brian Smith, Gwen Lomberk, Michael T. Zimmermann, Raul Urrutia
Summary: DOT1L, a unique histone lysine methyltransferase, plays a crucial role in blood cell biology and leukemogenesis by interacting with members of the AF protein family. Molecular dynamics studies reveal dynamic interactions between DOT1L, SAM, and H4, with more residues involved compared to static structures. Mutational analysis indicates key residues crucial for DOT1L function, providing insights into potential therapeutic targets.
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2021)
Article
Biochemistry & Molecular Biology
Eric M. Lewandowski, Kyle G. Kroeck, Lian M. C. Jacobs, Tyler G. Fenske, Robin N. Witt, Alyssa M. Hintz, Elizabeth R. Ramsden, Xiujun Zhang, Francis Peterson, Brian F. Volkman, Christopher T. Veldkamp, Yu Chen
Summary: This study presents the X-ray crystal structure of CCL19 and provides insights into its molecular features and potential receptor recognition sites. The computational analysis reveals differences in binding hotspots between CCL19 and CCL21.
Article
Chemistry, Medicinal
Daniel J. Sprague, Anthony E. Getschman, Tyler G. Fenske, Brian F. Volkman, Brian C. Smith
Summary: The CXCL12-CXCR4 signaling axis plays a critical role in development, immune function, and various diseases, including cancer and inflammatory diseases. A study has identified trisubstituted 1,3,5-triazines as competent ligands for the sY12-binding pocket of CXCL12, improving drug efficiency and offering new possibilities for therapeutic development and structural studies.
ACS MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Biochemistry & Molecular Biology
Acacia F. Dishman, Brian F. Volkman
Summary: Metamorphic proteins are single amino acid sequences that can reversibly convert between different conformations and have multiple functions. The challenges in this field include discovering more metamorphic proteins and designing new proteins that can switch conformations, which are important for disease treatment and protein-based therapies.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2022)
Article
Microbiology
Christian M. Berg, Michael R. Wedemeyer, Motiejus Melynis, Roman F. Schlimgen, Lasse Hansen, Jon F. Vabeno, Francis Peterson, Brian F. Volkman, Mette Rosenkilde, Hans F. Luettichau
Summary: This study investigates how the diversity of the UL146 gene in human cytomegalovirus (HCMV) affects its signaling and structural properties. The researchers find that certain genotypes exhibit similar functions despite lacking key structural domains, and many of the genotypes contain novel structural elements critical for protein folding. The findings highlight the host-adaptation of HCMV and propose novel structural interactions with implications for the virus-host interplay.
Article
Biochemistry & Molecular Biology
Holly N. Haver, Michael Wedemeyer, Erin Butcher, Francis C. Peterson, Brian F. Volkman, K. Matthew Scaglione
Summary: Protein aggregation is a key feature of polyglutamine diseases. This study focuses on understanding how serine-rich chaperone protein 1 (SRCP1) suppresses polyglutamine aggregation and its potential therapeutic implications. Through protein modeling and experimental validation, the study reveals the structural basis of SRCP1's inhibitory effect on protein aggregation and its mechanism of action. The findings also demonstrate that SRCP1 can inhibit aggregation of different polyglutamine-expanded proteins.
ACS CHEMICAL BIOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Acacia F. Dishman, Brian F. Volkman
Summary: Metamorphic proteins can switch between different stable structures with different functions, and they are not rare or transient exceptions to the 'one sequence, one fold' paradigm. The NusG family and the chemokine XCL1 are examples of metamorphic proteins that have preserved and optimized their folding over evolutionary time. Analysis of current protein families and resurrected protein ancestors shows that a large portion of sequence space is compatible with metamorphic folding. As a category that enhances biological fitness, metamorphic proteins are likely to utilize fold switching for important biological functions and may be more common than previously thought.
TRENDS IN BIOCHEMICAL SCIENCES
(2023)
Article
Biochemical Research Methods
Angela L. Zhou, Davin R. Jensen, Francis C. Peterson, Monica A. Thomas, Roman R. Schlimgen, Michael B. Dwinell, Brian C. Smith, Brian F. Volkman
Meeting Abstract
Biophysics
Brian F. Volkman
BIOPHYSICAL JOURNAL
(2020)