Article
Cell Biology
Cheng-Yao Chiang, Songqing Fan, Hongmei Zheng, Wenjun Guo, Zehan Zheng, Yihua Sun, Chuanqi Zhong, Juan Zeng, Shuaihu Li, Min Zhang, Tian Xiao, Duo Zheng
Summary: This study reveals the tumor-suppressive role of SETD7 in non-small cell lung cancer (NSCLC) by modulating KRAS methylation and degradation. SETD7 interacts with KRAS and methylates KRAS at lysines 182 and 184, leading to KRAS degradation and attenuation of the RAS/MEK/ERK signaling cascade.
Article
Biochemistry & Molecular Biology
Siman Gao, Xiangteng Zhao, Lin Hou, Ruining Ma, Jie Zhou, Michael X. Zhu, Si-Jian Pan, Yong Li
Summary: The study reveals that PKC delta is SUMOylated at lysine 473 in its C-terminal catalytic domain, increasing its stability by inhibiting ubiquitination. Additionally, a functional interplay between phosphorylation and SUMOylation of PKC delta strengthens the kinase's function through recruitment of SUMO E2/E3 ligases and the PKC delta kinase. Furthermore, the SUMOylation of PKC delta enhances apoptotic cell death induced by H2O2 by promoting protein stability and phosphorylation through an interdependent interplay of the PTMs.
Article
Cell Biology
Tadayuki Komori, Tomoki Kuwahara, Tetta Fujimoto, Maria Sakurai, Ikuko Koyama-Honda, Mitsunori Fukuda, Takeshi Iwatsubo
Summary: Recent studies have identified Rab29 as a Rab protein phosphorylated by LRRK2 and found that it is also phosphorylated under lysosomal overload stress. The phosphorylation site is Ser185 and this phosphorylation is involved in counteracting lysosomal enlargement. PKCα and PKCδ are involved in this phosphorylation and control the lysosomal localization of Rab29.
JOURNAL OF CELL SCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Fred Armbrust, Kira Bickenbach, Tomas Koudelka, Andreas Tholey, Claus Pietrzik, Christoph Becker-Pauly
Summary: Meprin beta is a zinc-dependent metalloprotease with a unique cleavage specificity for acidic amino acids at the cleavage site. Phosphorylation of meprin beta affects its cell surface activity and substrate cleavage extent, leading to internalization and degradation. The involvement of PKC isoforms in meprin beta phosphorylation was also demonstrated in this study.
Review
Cell Biology
Li-Min Mao, Nirav Mathur, Tayyibah Mahmood, Sri Rajan, Xiang-Ping Chu, John Q. Wang
Summary: This review summarizes recent progress in research on phosphorylation and phosphorylation-dependent regulation of group II metabotropic glutamate receptors. It includes detailed mapping of phosphorylation sites and the roles of protein kinases and phosphatases. Additionally, the potential linkage of mGlu2/3 phosphorylation to neurological and neuropsychiatric disorders is explored, and future research directions are discussed.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Guadalupe Garcia, Karina A. Mendez-Resendiz, Norma Oviedo, Janet Murbartian
Summary: PKC and PKA phosphorylation inhibit TREK-1 channels downstream of G(s) protein-coupled receptor activation in vitro. This study investigated the role of phosphorylation of TREK-1 in neuropathic pain, finding that PKC and PKA modulators can alter TREK-1 function to contribute to antiallodynia in neuropathic rats, potentially through the phosphorylation sites S300 and S333.
JOURNAL OF NEUROCHEMISTRY
(2021)
Article
Neurosciences
Zhaoyang Li, Wenhao Dong, Xinyuan Zhang, Jun-Mei Lu, Yan-Ai Mei, Changlong Hu
Summary: The study demonstrates that PKC activation inhibits Kv2.2 channel currents and alters their steady-state activation, showing that the function of Kv2.2 is dependent on its phosphorylation state. In cortical slices, PKC activation reduces the frequency of action potentials by regulating Kv2.2 channels.
NEUROSCIENCE BULLETIN
(2022)
Article
Biochemistry & Molecular Biology
Eric Herrmann, Lars Langemeyer, Kathrin Auffarth, Christian Ungermann, Daniel Kuemmel
Summary: This study identifies and characterizes an amphipathic helix in Ccz1 that plays a crucial role in autophagy. Membrane binding and interaction with recruiter proteins collectively regulate the membrane recruitment of MC1, and specific protein and lipid cues convey the differential targeting of MC1 to distinct target compartments.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Eva Wisniewski, Domonkos Czaran, Fanni Kovacs, Eniko Bahurek, Afrodite Nemeth, Peter Sasvari, Gergo Szanda, Aladar Pettko-Szandtner, Eva Klement, Erzsebet Ligeti, Roland Csepanyi-Komi
Summary: This study reveals the regulatory role of different phosphorylation patterns on the GAP activity, superoxide production, and phagocytic effect of ARHGAP25.
Article
Chemistry, Medicinal
Jae Seok Yoon, Hyo-Jung Lee, Deok Yong Sim, Eunji Im, Ji Eon Park, Woon Yi Park, Ja Il Koo, Bum Sang Shim, Sung-Hoon Kim
Summary: Moracin D induces apoptosis in DU145 prostate cancer cells through activation of PPAR-gamma/p-PKC-delta signaling and inhibition of p-PKC-alpha. It downregulates caspase-3 and PARP expression, with DU145 cells showing higher sensitivity compared to PC3 cells. This highlights a novel mechanism by which Moracin D exerts its cytotoxic effects in prostate cancer.
PHYTOTHERAPY RESEARCH
(2021)
Article
Cell Biology
Renato Socodato, Artur Rodrigues-Santos, Joana Tedim-Moreira, Tiago O. Almeida, Teresa Canedo, Camila C. Portugal, Joao B. Relvas
Summary: Microglia, the largest myeloid cell population in the brain, play a crucial role in regulating the response and survival during inflammation. RhoA activity is essential for microglial metabolic reprogramming and their reaction to inflammation.
CELL DEATH & DISEASE
(2023)
Article
Biochemistry & Molecular Biology
Cheng Zhang, Theresa Lauster, Wenxin Tang, Anaxi Houbaert, Shanshuo Zhu, Dominique Eeckhout, Ive De Smet, Geert De Jaeger, Thomas B. Jacobs, Tongda Xu, Sabine Mueller, Eugenia Russinova
Summary: In this study, it was found that brassinosteroid (BR) influences Arabidopsis epidermal cell morphogenesis by regulating PLECKSTRIN HOMOLOGY GTPase-ACTIVATING proteins (PHGAPs), thereby connecting the BR and ROP2-GTPase signaling pathways crucial for pavement cell interdigitation.
Article
Biochemistry & Molecular Biology
Renpeng Zhou, Yong Chen, Shufang Li, Xin Wei, Weirong Hu, Suan Tang, Jie Ding, Wanjin Fu, Hailin Zhang, Fan Chen, Wenjuan Hao, Yi Lin, Rendi Zhu, Ke Wang, Lei Dong, Yingjie Zhao, Xiaowen Feng, Feihu Chen, Changhai Ding, Wei Hu
Summary: This study identified the role of TRPM7 channel-mediated chondrocyte ferroptosis in the destruction of articular cartilage associated with rheumatoid arthritis (RA). The findings suggest that TRPM7-mediated chondrocyte ferroptosis is a promising target for the prevention and treatment of RA through the PKC alpha-NOX4 axis.
Article
Biochemistry & Molecular Biology
Xinyue Li, Navneet Kaur, Mustafa Albahrani, Adam R. Karpf, Adrian R. Black, Jennifer D. Black
Summary: This study identified a novel crosstalk between PKC alpha and TGF beta signaling, which regulates the expression of TGF beta receptor 1 and affects intestinal epithelial cell proliferation and tumor development. The crosstalk between PKC alpha and TGF beta signaling is not only present in the intestine, but also in other epithelial tissues.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Review
Pharmacology & Pharmacy
Timothy R. Baffi, Ksenya Cohen-Katsenelson, Alexandra C. Newton
Summary: While protein kinases have been successfully targeted for diseases, protein phosphatases have not been utilized as therapeutic targets due to incomplete understanding of their effects on signaling networks. PHLPP, a relatively new player in cell signaling, has roles in cell survival, proliferation, and apoptosis, and recent research suggests it may have opposing effects in promoting cell survival. Additionally, PHLPP has been identified as a critical mediator of transcriptional programs in cancer and inflammation.
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 61, 2021
(2021)
Article
Multidisciplinary Sciences
Jolanta Bondaruk, Roman Jaksik, Ziqiao Wang, David Cogdell, Sangkyou Lee, Yujie Chen, Khanh Ngoc Dinh, Tadeusz Majewski, Li Zhang, Shaolong Cao, Feng Tian, Hui Yao, Pawek Kus, Huiqin Chen, John N. Weinstein, Neema Navai, Colin Dinney, Jianjun Gao, Dan Theodorescu, Christopher Logothetis, Charles C. Guo, Wenyi Wang, David McConkey, Peng Wei, Marek Kimmel, Bogdan Czerniak
Summary: Whole-organ mapping identified dysregulated pathways and immune response involvement in bladder cancer development. Aberrant methylation/expression of genes and different types of mutations were found to be associated with disease progression. The carcinogenesis process can be divided into dormant and progressive phases.
Review
Oncology
Christa M. Lam, Zihai Li, Dan Theodorescu, Xue Li
Summary: The incidence of bladder cancer is higher in males than females, regardless of geographical, racial, or socioeconomic factors. Despite potential differences in tumor biology, male and female bladder cancer patients are managed similarly. Advances in genomic technology have shed light on complex sex-biasing factors such as epigenetics, single nucleotide polymorphism, metabolism, and immunity. Understanding sex-biasing effects can inform precision medicine efforts based on a patient's biological sex.
Review
Urology & Nephrology
Michael Nazmifar, Cheyenne Williams, Aurash Naser-Tavakolian, John Heard, Charles Rosser, Dan Theodorescu, Michael Ahdoot
Summary: The purpose of this study is to evaluate the efficacy of various therapeutic agents for high-grade nonmuscle-invasive bladder cancer following failed bacillus Calmette-Guerin treatment. A systematic review of available clinical trials was conducted, and a total of 70 studies evaluating 27 treatment options were analyzed. Intravesical chemotherapy and hyperthermia paired with chemotherapy demonstrated high complete response rates, while immunotherapy and novel agents also showed promising results. The treatments had low toxicity profiles and complication rates.
JOURNAL OF UROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Christian Soehngen, David J. Thomas, Margaretha A. Skowron, Felix Bremmer, Markus Eckstein, Anja Stefanski, Marc D. Driessen, Gamal A. Wakileh, Kai Stuehler, Peter Altevogt, Dan Theodorescu, Ruediger Klapdor, Axel Schambach, Daniel Nettersheim
Summary: This study aimed to understand the molecular function of CD24 in vitro and evaluate the cytotoxic capacity of NK cell CAR against CD24 in urological tumor cells. The results showed that CD24 interacts with proteins involved in cell adhesion, ATP binding, phosphoprotein binding, and post-translational modifications. Treatment with NK-CD24-CAR cells significantly decreased cell viability and induced apoptosis specifically in CD24(+) tumor cells. This study provides a promising novel target for immune therapeutic approaches against urological malignancies.
Article
Multidisciplinary Sciences
Hany A. Abdel-Hafiz, Johanna M. Schafer, Xingyu Chen, Tong Xiao, Timothy D. Gauntner, Zihai Li, Dan Theodorescu
Summary: Loss of the Y chromosome (LOY) correlates with poor prognoses in bladder cancer patients. LOY mutations alter T cell function, promoting T cell exhaustion and sensitizing them to PD-1-targeted immunotherapy.
Article
Cell Biology
Florus C. de Jong, Teemu D. Laajala, Robert F. Hoedemaeker, Kimberley R. Jordan, Angelique C. J. van der Made, Egbert R. Boeve, Deric K. E. van der Schoot, Bart Nieuwkamer, Emiel A. M. Janssen, Tokameh Mahmoudi, Joost L. Boormans, Dan Theodorescu, James C. Costello, Tahlita C. M. Zuiverloon
Summary: The recommended treatment for high-risk non-muscle-invasive bladder cancer patients is tumor resection followed by adjuvant Bacillus Calmette-Guerin (BCG) bladder instillations. However, only 50% of patients benefit from this therapy. Identifying tumors unlikely to respond to BCG can lead to alternative treatments for these patients.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Review
Oncology
Peris R. Castaneda, Dan Theodorescu, Charles J. Rosser, Michael Ahdoot
Summary: Bladder cancer is a complex disease with variable prognosis, and recent studies have identified frequent genetic alterations and molecular subtypes. Personalized treatment strategies and the development of biomarkers to predict response and guide therapy in bladder cancer have become a focus of research. In this review, we summarize the latest studies on novel biomarkers in bladder cancer, specifically those intended to improve risk stratification and treatment selection, based on a search of recently published PubMed articles using relevant keywords.
FRONTIERS IN ONCOLOGY
(2023)
Article
Urology & Nephrology
Thomas W. Flaig, Catherine M. Tangen, Siamak Daneshmand, Ajjai Shivaram Alva, M. Scott Lucia, David James McConkey, Dan Theodorescu, Amir Goldkorn, Matthew I. Milowsky, Rick Bangs, Gary R. MacVicar, Bruno R. Bastos, Jared S. Fowles, Daniel L. Gustafson, Melissa Plets, Ian M. Thompson Jr, Seth P. Lerner
Summary: This article mainly evaluated the predictive role of the COXEN gene expression model in neoadjuvant chemotherapy for bladder cancer, and conducted a secondary analysis of the association between COXEN scores and event-free survival and overall survival.
Article
Biology
Ruben Rosas, Rhiannon R. Aguilar, Nina Arslanovic, Anna Seck, Duncan J. Smith, Jessica K. Tyler, Mair E. A. Churchill
Summary: The histone chaperone CAF-1 deposits histone H3/H4 dimers onto newly replicated DNA to form the central core of the nucleosome tetrasome. The KER SAH region of CAF-1 plays a crucial role in ensuring the assembly of tetrasomes by linking functional domains within CAF-1 with structural precision.
Review
Medicine, General & Internal
Lars Dyrskjot, Donna E. Hansel, Jason A. Efstathiou, Margaret A. Knowles, Matthew D. Galsky, Jeremy Teoh, Dan Theodorescu
Summary: Bladder cancer is a global health issue with distinct molecular subtypes and pathogenic pathways. Early detection and diagnosis are crucial for improving patient outcomes. Treatment options vary depending on the invasion level and include surgery and immunotherapy. Effective management requires a multidisciplinary approach that considers patient characteristics and molecular disease characteristics.
NATURE REVIEWS DISEASE PRIMERS
(2023)
Article
Multidisciplinary Sciences
Hany A. Abdel-Hafiz, Saravana Kumar Kailasam Mani, Wesley Huang, I. I. I. Kenneth H. Gouin, Yuzhou Chang, Tong Xiao, Qin Ma, Zihai Li, Simon R. V. Knott, Dan Theodorescu
Summary: In this study, single-cell RNA sequencing was used to characterize cell-type specific transcriptional differences between male and female BBN-induced tumors. Proportional and gene expression differences were found in epithelial and non-epithelial subpopulations between male and female tumors. Several genes were found to predict sex-specific survival in human BLCA datasets. Novel and clinically relevant sex-specific transcriptional signatures were identified, including immune cells in the tumor microenvironment. It validated the relevance of the BBN model for studying sex differences in human BLCA.
Review
Urology & Nephrology
Jun Gong, Daniel M. Kim, Michael R. Freeman, Hyung Kim, Leigh Ellis, Bethany Smith, Dan Theodorescu, Edwin Posadas, Robert Figlin, Neil Bhowmick, Stephen J. Freedland
Summary: Black men with prostate cancer have biologically distinct cancers compared to white men, including genetic alterations, protein differences, and tumor microenvironment. Socioeconomic status partially explains the disparities, but not completely. Further research on these biological differences can guide efforts to improve treatment outcomes for Black men.
NATURE REVIEWS UROLOGY
(2023)
Meeting Abstract
Oncology
Matthew Mackay, Nicholas Mitsiades, Young Kwang Chae, Andrew A. Davis, Philip Edward Lammers, James F. Maher, Dan Theodorescu, Peter Rubin, Timothy J. Pluard, Lee Langer, Kabir Manghnani, Rotem Ben-Shachar, Kimberly L. Blackwell, James Lin Chen, Joel Dudley, Justin Guinney, Wade Thomas Iams
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Sebastien Rinaldetti, Qiong Zhou, Joshua M. Abbott, Florus C. de Jong, Hector Esquer, James C. Costello, Dan Theodorescu, Daniel LaBarbera
Summary: This study discovered novel subtype-stratified therapy approaches for bladder cancer based on high-content screening, and correlated drug sensitivity with functional genomics to validate and understand the underlying mechanisms.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Meeting Abstract
Urology & Nephrology
Jong F. C. De, T. D. Laajala, R. F. Hoedemaeker, S. Rinaldetti, K. Jordan, A. C. J. Van der Made, B. Nieuwkamer, E. R. Boeve, E. A. M. Janssen, T. Mahmoudi, J. L. Boormans, D. Theodorescu, J. C. Costello, T. C. M. Zuiverloon