Advancements in MS-based phospho-proteomics techniques have helped uncover hundred thousands of protein phosphorylation sites in human and various model organisms. The majority of these sites are uncharacterized. The sheer number of uncharacterized sites necessitates systematic approaches to prioritize sites for more in-depth annotation. Analyzing the phosphorylation and sequence conservation of uncharacterized sites across species can help reveal a subset of the functionally important phosphorylation events. Here, we outline the workflow and provide an overview of publicly available computational resources for conservation analysis of novel phosphorylation sites.
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http://dx.doi.org/10.1007/978-1-4939-7154-1_29 | DOI Listing |
Clin Cancer Res
January 2025
Stanford University, Palo Alto, CA, United States.
Purpose: After failing primary and secondary hormonal therapy, castration-resistant and neuroendocrine prostate cancer metastatic to the bone is invariably lethal, although treatment with docetaxel and carboplatin can modestly improve survival. Therefore, agents targeting biologically relevant pathways in PCa and potentially synergizing with docetaxel and carboplatin in inhibiting bone metastasis growth are urgently needed.
Experimental Design: Phosphorylated (activated) AXL expression in human prostate cancer bone metastases was assessed by immunohistochemical staining.
Proc Natl Acad Sci U S A
February 2025
Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada.
ClpXP is a two-component mitochondrial matrix protease. The caseinolytic mitochondrial matrix peptidase chaperone subunit X (ClpX) recognizes and translocates protein substrates into the degradation chamber of the caseinolytic protease P (ClpP) for proteolysis. ClpXP degrades damaged respiratory chain proteins and is necessary for cancer cell survival.
View Article and Find Full Text PDFJ Med Chem
January 2025
Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, 12850 East Montview Boulevard, Aurora, Colorado 80045, United States.
AMP-activated protein kinase (AMPK) is a central mediator of cellular metabolism and is activated in direct response to low ATP levels. Activated AMPK inhibits anabolic pathways and promotes catabolic activities that generate ATP through the phosphorylation of multiple target substrates. AMPK is a therapeutic target for activation in several chronic metabolic diseases, and there is increasing interest in targeting AMPK activity in cancer where it can act as a tumor suppressor or conversely it can support cancer cell survival.
View Article and Find Full Text PDFJ Vis Exp
January 2025
Institute of Biochemistry and Molecular Biology, Hengyang Medical School, University of South China; National Health Commission Key Laboratory of Birth Defect Research and Preventio, Hunan Provincial Maternal and Child Health Care Hospital;
Both DNA replication and RNA transcription utilize genomic DNA as their template, necessitating spatial and temporal separation of these processes. Conflicts between the replication and transcription machinery, termed transcription-replication conflicts (TRCs), pose a considerable risk to genome stability, a critical factor in cancer development. While several factors regulating these collisions have been identified, pinpointing primary causes remains difficult due to limited tools for direct visualization and clear interpretation.
View Article and Find Full Text PDFJ Cancer Res Clin Oncol
January 2025
Key Laboratory of Laboratory Medicine, Ministry of Education of China, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China.
Purpose: Growing evidence suggests that the tyrosine phosphatase SHP2 is pivotal for tumor progression. Triple-negative breast cancer (TNBC) is the most lethal subtype of breast cancer, characterized by its high recurrence rate, aggressive metastasis, and resistance to chemotherapy. Understanding the mechanisms of tumorigenesis and the underlying molecular pathways in TNBC could aid in identifying new therapeutic targets.
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