Editorial Material
Multidisciplinary Sciences
Mark R. Woodford, Dimitra Bourboulia, Mehdi Mollapour
Summary: Molecular chaperones play a crucial role in establishing important protein-protein interaction networks, which are often enriched in certain diseases. A study published in Nature Communications used epichaperomics to identify unique changes occurring in chaperone-formed protein networks during mitosis in cancer cells.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Xiao-lian Liu, Gui-ming Zhang, Si-si Huang, Wen-hui Shi, Lin-xuan Ye, Zhong-lu Ren, Jia-jie Zhang, Shu-wen Liu, Le Yu, Yi-lei Li
Summary: PTEN loss correlates with hypersensitivity to rapalogs in ccRCC cells and could be a marker for rapalog therapy selection in ccRCC patients.
ACTA PHARMACOLOGICA SINICA
(2022)
Article
Chemistry, Multidisciplinary
Nam Gu Yoon, Hakbong Lee, So-Yeon Kim, Sung Hu, Darong Kim, Sujae Yang, Ki Bum Hong, Ji Hoon Lee, Soosung Kang, Byung-Gyu Kim, Kyungjae Myung, Changwook Lee, Byoung Heon Kang
Summary: The study identified Mitoquinone (MitoQ) as a potent inhibitor of mitochondrial Hsp90, offering potential anticancer properties. By competitively binding with TRAP1 clients, MitoQ facilitated the identification of mitochondrial protein interactions. Targeting the client binding site of Hsp90 family proteins provides a novel strategy for developing potent anticancer drugs.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Medicinal
Mengyang Xu, Chao Zhao, Biying Zhu, Liangyue Wang, Huihao Zhou, Daoguang Yan, Qiong Gu, Jun Xu
Summary: The study introduces a new method for discovering potent Hsp90 inhibitors by assembling fragments, providing a novel approach for finding anti-nasopharyngeal carcinoma agents. Through chemotyping analysis and click chemistry, 15 anti-Hsp90 fragments were identified, 21 compounds were synthesized, and the more potent 4f inhibitor was discovered.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Ondrej Mitrovsky, Denisa Myslivcova, Tereza Machackova-Lopotova, Adam Obr, Kamila Cermakova, Sarka Ransdorfova, Jana Brezinova, Hana Klamova, Marketa Zackova
Summary: Chronic myelogenous leukemia (CML) is a myeloproliferative disease characterized by the BCR-ABL oncogene. Despite the high performance of treatment with tyrosine kinase inhibitors (TKI), about 30% of patients develop resistance to the therapy. In this study, the researchers identified Casein Kinase 2 (CK2) as a potential target for CML therapy. They established new CML cell lines resistant to TKIs and found that CK2 activation was increased in these cells. Inhibition of CK2 using CX-4945 induced cell death in both parental and resistant CML cell lines, suggesting that CK2 represents a potential target for CML treatment.
Article
Biochemistry & Molecular Biology
Yunhan Jiang, Lina Song, Yizhu Lin, Pawel Nowialis, Qiongmei Gao, Tao Li, Bin Li, Xiaobo Mao, Qianqian Song, Chengguo Xing, Guangrong Zheng, Shuang Huang, Lingtao Jin
Summary: Ovarian cancer is a deadly gynecological malignancy and platinum-based chemotherapy is the primary treatment. However, the development of platinum resistance contributes to recurrence and mortality. In this study, researchers identified SRMS as a negative regulator of MKK4-JNK signaling under platinum treatment in ovarian cancer. Inhibiting SRMS sensitized p53-deficient cancer cells to platinum and enhanced apoptosis. Furthermore, a repurposed drug, PLX4720, was found to be a potent SRMS inhibitor that increased the efficacy of platinum-based chemotherapy. Targeting SRMS with PLX4720 could overcome chemoresistance in ovarian cancer.
Article
Oncology
Yan Sun, Liang Zhu, Pian Liu, Huan Zhang, Feng Guo, Xin Jin
Summary: In this study, researchers found that the upregulation of palmitoyl acyltransferase ZDHHC2 is associated with TKI resistance in ccRCC. ZDHHC2 mediates AGK S-palmitoylation to activate the PI3K-AKT-mTOR signaling pathway, which modulates sunitinib sensitivity. These findings suggest that targeting ZDHHC2 may improve the efficacy of sunitinib in treating ccRCC.
Article
Biology
Xiaolong Tang, Lizhi Cheng, Guo Li, Yong-Ming Yan, Fengting Su, Dan-Ling Huang, Shuping Zhang, Zuojun Liu, Minxian Qian, Ji Li, Yong-Xian Cheng, Baohua Liu
Summary: The small molecule compound D6 demonstrates promising efficacy in treating EGFR-TKI resistant NSCLC by targeting the protein-protein interaction between HSP90 and T790M-EGFR, offering a potential alternative strategy to overcome drug resistance.
COMMUNICATIONS BIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Kai-long Jiang, Le-xian Tong, Tao Wang, Han-lin Wang, Xiao-bei Hu, Gao-ya Xu, Ting-ting Jin, Wei-juan Kan, Lei Xu, Jia-nan Li, Kai-xiang Zhang, Ning Song, Jie-yu Liu, Meng-meng Zhang, Wen-biao Wu, Yu-qi Xiang, An-hui Gao, Yong-zhou Hu, Yu-bo Zhou, Tao Liu, Jian-min Yang, Jia Li
Summary: The study demonstrates that hematologic malignancies are more sensitive to CHK1i than solid tumors, and downregulation of c-Myc may represent the efficacy of CHK1i in hematologic malignancies.
ACTA PHARMACOLOGICA SINICA
(2022)
Article
Pharmacology & Pharmacy
Mei Chen, Zhenyu Nie, Yuanhui Gao, Hui Cao, Linlin Zheng, Na Guo, Yanling Peng, Shufang Zhang
Summary: This study revealed the role of m7G RNA methylation in the tumor immune microenvironment of KIRC and developed an m7G score that can predict patient prognosis. Experimental evidence showed that knocking down WDR4 can inhibit KIRC cell proliferation, migration, invasion, and increase sensitivity to specific drugs.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Kunping Li, Linyi Tan, Yuqing Li, Yinfeng Lyu, Xinyi Zheng, Haowen Jiang, Xiaohua Zhang, Hui Wen, Chenchen Feng
Summary: This study comprehensively investigates the characteristics of cuproptosis in clear-cell renal cell carcinoma (ccRCC) and finds that decreased cuproptosis is associated with better prognosis. It also reveals the relationship between cuproptosis and increased tricarboxylic acid cycle activity and decreased hypoxia signaling.
Article
Oncology
Francisco Exposito, Miriam Redrado, Maeva Houry, Katherine Hastings, Magdalena Molero-Abraham, Teresa Lozano, Jose Luis Solorzano, Julian Sanz-Ortega, Vera Adradas, Ramon Amat, Esther Redin, Sergio Leon, Naroa Legarra, Javier Garcia, Diego Serrano, Karmele Valencia, Camila Robles-Oteiza, Giorgia Foggetti, Nerea Otegui, Enriqueta Felip, Juan J. Lasarte, Luis Paz-Ares, Jon Zugazagoitia, Katerina Politi, Luis Montuenga, Alfonso Calvo
Summary: Immunotherapy resistance in non-small cell lung cancer (NSCLC) can be attributed to an immunosuppressive microenvironment created by genetic alterations in the PTEN/PI3K/AKT/mTOR pathway and/or loss of PTEN expression. PTEN-low tumors are associated with higher levels of immune checkpoint proteins and poorer response to immunotherapy. Preclinical models demonstrate that PTEN loss promotes metastasis and fibrosis, and facilitates the conversion of immune cells into immunosuppressive regulatory T cells (Treg). However, targeting PTEN loss-mediated immunosuppression can reverse immunotherapy resistance in NSCLC.
Article
Biology
Weinan Zheng, Liang Cui, Minghui Li, Yun Li, Wenhui Fan, Limin Yang, Jing Li, Lei Sun, Wenjun Liu
Summary: The study identified a novel strain of influenza A virus with cold sensitivity conferred by a mutation in the phosphorylation site within the nucleoprotein. The mutation led to reduced replicative capacity of the virus in low temperatures, attributed to diminished NP oligomerization. This suggests that the phosphorylation of NP may play a critical role in regulating the temperature sensitivity of influenza A virus.
SCIENCE CHINA-LIFE SCIENCES
(2021)
Article
Cell Biology
Xinfang Yu, Li Zhou, Wenbin Liu, Lijun Liu, Feng Gao, Wei Li, Haidan Liu
Summary: Skp2 is highly expressed in human colorectal cancer and plays a role in promoting tumorigenesis by stabilizing Mcl-1. Blocking Skp2 expression reduces tumorigenic properties of CRC cells, while Skp2 deficiency enhances sensitivity of CRC cells to irradiation treatments.
CELL DEATH & DISEASE
(2022)
Article
Oncology
Caiyu Sun, Weiqiang Jing, Gaozhong Xiong, Dapeng Ma, Yueke Lin, Xiaoting Lv, Yunxue Zhao, Xiaomin Ma, Lihui Zhu, Xuecheng Shen, Min Yang, Zhenzhi Qin, Yeping Cheng, Haocheng Xuan, Tao Li, Lihui Han
Summary: This study identified Src and PARP1 as novel synthetic lethal partners, and the combination therapy showed significant anti-tumor effects without causing obvious side effects. The findings suggest that targeting both PARP1 and Src may broaden the strategies for HCC treatment and benefit patients with high Src activation and resistance to PARP1 inhibitors alone.
Article
Oncology
Olga Lakiza, Julian Lutze, Alyx Vogle, Jelani Williams, Abde Abukdheir, Paul Miller, Chih-Yi 'Andy' Liao, Sean P. Pitroda, Carlos Martinez, Andrea Olivas, Namrata Setia, Stephen J. Kron, Ralph R. Weichselbaum, Xavier M. Keutgen
Summary: This study shows that MEN1 loss of function increases the radiosensitivity of PanNETs, potentially due to defects in DNA double-strand break repair and reduced BRCA2 expression. Combining radiation therapy with the PARP inhibitor talazoparib may be beneficial for patients with PanNETs and MEN1 loss of function.
ENDOCRINE-RELATED CANCER
(2022)
Letter
Pathology
Sanjay A. Pai, Bidisha Bhaduri, Supraja Chandrasekar, Phalguni Anand Alladi, Tiffany Caza, Anita Mahadevan, T. R. Saiprasad, Patrick Walker
JOURNAL OF CLINICAL PATHOLOGY
(2022)
Article
Multidisciplinary Sciences
Manisha Krishnan, Madhavi D. Senagolage, Jeremy T. Baeten, Donald J. Wolfgeher, Saira Khan, Stephen J. Kron, Megan E. McNerney
Summary: CUX1 is often deleted or mutated in various tumors, but it acts as a tumor suppressor in hematopoietic cells. Previous studies suggested an oncogenic role of CUX1 in solid tumors, but our research found no evidence to support this hypothesis.
SCIENTIFIC REPORTS
(2022)
Editorial Material
Biochemistry & Molecular Biology
Siddhi Omkar, Andrew W. Truman
Summary: The study uncovers the minimal requirements for chaperone-mediated dispersal of Pab1 biomolecular condensates, expanding our understanding of the uniqueness of co-chaperones and deepening our fundamental knowledge of the heat shock response in cells.
TRENDS IN BIOCHEMICAL SCIENCES
(2022)
Article
Genetics & Heredity
Laura E. Knighton, Nitika, Siddhi Omkar, Andrew W. Truman
Summary: Hsp70 family of molecular chaperones is well-conserved and expressed in all organisms. In budding yeast, cells express four highly similar cytosolic Hsp70s Ssa1, 2, 3 and 4 which arose from gene duplication. Recent evidence suggests that despite their amino acid similarity, these Ssas have unique roles in the cell. Here we examine the relative importance of Ssa1-4 in the regulation of the enzyme ribonucleotide reductase (RNR). We demonstrate that cells expressing either Ssa3 or Ssa4 as their sole Ssa are compromised for their resistance to DNA damaging agents and activation of DNA damage response (DDR)-regulated transcription. In addition, we show that the steady state levels and stability of RNR small subunits Rnr2 and Rnr4 are reduced in Ssa3 or Ssa4-expressing cells, a result of decreased Ssa-RNR interaction. Interaction between the Hsp70 co-chaperone Ydj1 and RNR is correspondingly decreased in cells only expressing Ssa3 and 4. Through studies of Ssa2/4 domain swap chimeras, we determined that the C-terminal domain of Ssas are the source of this functional specificity. Taking together, our work suggests a distinct role for Ssa paralogs in regulating DNA replication mediated by C-terminus sequence variation.
Article
Biochemistry & Molecular Biology
Siddhi Omkar, Tasaduq H. Wani, Bo Zheng, Megan M. Mitchem, Andrew W. Truman
Summary: This study shows that APE2 and Apn2 proteins depend on the chaperone system in yeast and mammalian cells, and suggests that inhibiting chaperones may be a potential anticancer therapy targeting APE2-mediated processes.
Article
Multidisciplinary Sciences
Amy Flor, Joanna Pagacz, DeShawn Thompson, Stephen Kron
Summary: Cellular senescence is a state of proliferative arrest induced by biological damage that normally occurs in aging cells over time, but it can also rapidly occur in tumor cells as a response to damage. Tumor cell senescence is generally undesirable as it leads to resistance to death and hinders tumor remission, increasing tumor malignancy and treatment resistance. The identification of senescent tumor cells is of ongoing interest to the cancer research community. Various senescence assays exist, many based on the activity of the well-known senescence marker, senescence-associated beta-galactosidase (SA-beta-Gal).
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2022)
Editorial Material
Biochemistry & Molecular Biology
Siddhi Omkar, Ainella Rysbayeva, Andrew W. Truman
Summary: The interactions between molecular chaperones and their clients can be influenced by post-translational modifications (PTMs) on chaperones, known as the 'chaperone code'. However, it is still not well understood how PTMs on client proteins may affect chaperone-client interactions. In this forum, we explore the potential of a 'client code' that may play a role in these interactions.
TRENDS IN BIOCHEMICAL SCIENCES
(2023)
Article
Oncology
Yue Liu, Joanna Pagacz, Donald J. Wolfgeher, Kenneth D. Bromerg, Jacob Gorman, Stephen J. Kron
Summary: Antigen presentation may be the limiting factor in the low immune response to radiation therapy, and combining immune checkpoint blockade does not restore cytotoxic T lymphocytes function. Therapeutic vaccines based on senescent tumor cells or SnC-activated dendritic cells have the potential to enhance immune therapies and limit recurrence or metastasis.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Editorial Material
Biochemistry & Molecular Biology
Chrisostomos Prodromou
Article
Pathology
William G. Stetler-Stevenson
Summary: Tissue inhibitors of metalloproteinases (TIMPs) are a family of proteins that inhibit matrixin proteinases and demonstrate unique non-protease-mediated functions. Among them, TIMP2 shows potential tumor suppressor activity and can modulate cell signaling pathways, impacting cell proliferation and migration.
AMERICAN JOURNAL OF PATHOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Sasha Coates-Park, Carolyn Lazaroff, Sadeechya Gurung, Josh Rich, Alexandra Colladay, Maura O'Neill, Georgina S. Butler, Christopher M. Overall, William G. Stetler-Stevenson, David Peeney
Summary: Extracellular proteolysis and turnover play crucial roles in tissue homeostasis. MMPs, as the main matrix-degrading enzymes, are regulated by TIMPs. The balance between MMP activity and TIMP levels is essential for healthy tissue homeostasis and can be disrupted in pathological conditions.
Editorial Material
Multidisciplinary Sciences
Mark R. Woodford, Dimitra Bourboulia, Mehdi Mollapour
Summary: Molecular chaperones play a crucial role in establishing important protein-protein interaction networks, which are often enriched in certain diseases. A study published in Nature Communications used epichaperomics to identify unique changes occurring in chaperone-formed protein networks during mitosis in cancer cells.
NATURE COMMUNICATIONS
(2023)
Article
Biochemical Research Methods
Yue Liu, Stephen J. Kron
Summary: This article presents a protocol for examining the ability of therapy-induced senescence (TIS) to stimulate the activation of type 1 conventional CD103+ dendritic cells (DCs). The protocol includes steps for isolating and differentiating CD103+ DCs, inducing cell senescence, coculturing cells, and analyzing cell maturation and activation using flow cytometry.
