Protein phosphatase activity acts as a primary determinant of the extent and duration of phosphorylation of cellular proteins in response to physiological stimuli. Ser/Thr protein phosphatase-1 (PP1) belongs to the PPP superfamily, and is associated with regulatory subunits that confer substrate specificity, allosteric regulation, and subcellular compartmentalization. In addition, all eukaryotic cells contain multiple heat-stable proteins that originally were thought to inhibit phosphatase catalytic subunits released from the regulatory subunits, as a fail-safe mechanism. However, discovery of C-kinase-activated PP1 inhibitor, Mr of 17 kDa (CPI-17) required fresh thinking about the endogenous inhibitors as specific regulators of particular phosphatase complexes, acting in addition to, not instead of, regulatory subunits. The cellular actions of the endogenous inhibitors are controlled by phosphorylation, connecting them to kinase pathways. More recent progress has unveiled additional functions of PP1 inhibitor-2 (I-2), including regulation of protein kinases. Transcriptional mechanisms govern the expression levels of CPI-17 in response to stimuli. If true for other inhibitor proteins, they have the potential of being diagnostic markers for pathological conditions. We discuss specific examples of PP1 inhibitor proteins regulating particular cellular functions and the rationale for incorporating phosphatase inhibitor proteins in development of new therapeutic strategies.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3422418 | PMC |
http://dx.doi.org/10.1002/iub.1067 | DOI Listing |
Cell Commun Signal
January 2025
Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, 100191, China.
Background: Ovarian cancer (OC), particularly high-grade serous ovarian carcinoma (HGSOC), is the leading cause of mortality from gynecological malignancies worldwide. Despite the initial effectiveness of treatment, acquired resistance to poly(ADP-ribose) polymerase inhibitors (PARPis) represents a major challenge for the clinical management of HGSOC, highlighting the necessity for the development of novel therapeutic strategies. This study investigated the role of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), a pivotal regulator of glycolysis, in PARPi resistance and explored its potential as a therapeutic target to overcome PARPi resistance.
View Article and Find Full Text PDFSci Rep
January 2025
Division of Hematology, Second Xiang-ya Hospital, Central South University, Changsha, China.
Acute B-lymphoblastic leukemia (B-ALL) is a highly heterogeneous hematologic malignancy, characterized by significant molecular differences among patients as the disease progresses. While the PI3K-Akt signaling pathway and metabolic reprogramming are known to play crucial roles in B-ALL, the interactions between lipid metabolism, immune pathways, and drug resistance remain unclear. In this study, we performed multi-omics analysis on different patient cohorts (newly diagnosed, relapsed, standard-risk, and poor-risk) to investigate the molecular characteristics associated with metabolism, signaling pathways, and immune regulation in B-ALL.
View Article and Find Full Text PDFSci Rep
January 2025
School of Stomatology, Bengbu Medical University, No. 2600 Donghai Road, Bengbu, 233030, China.
Tongue squamous cell carcinoma (TSCC) is a common malignant oral cancer characterized by substantial invasion, a high rate of lymph node and distant metastasis, and a high recurrence rate. This study aims to provide new ideas for the diagnosis and treatment of TSCC patients by exploring the related mechanisms that affect the migration and invasion of TSCC and inhibit the migration and spread of cancer cells. The results indicated the rate of high expression of IL-17 in cancer tissues was greater than that in tongue tissues, and the expression of IL-17 was related to the TNM stage.
View Article and Find Full Text PDFSci Rep
January 2025
Department of Genetics, The University of Alabama at Birmingham, Birmingham, AL, USA.
Nowadays, chemotherapy and immunotherapy remain the major treatment strategies for Triple-Negative Breast Cancer (TNBC). Identifying biomarkers to pre-select and subclassify TNBC patients with distinct chemotherapy responses is essential. In the current study, we performed an unbiased Reverse Phase Protein Array (RPPA) on TNBC cells treated with chemotherapy compounds and found a leading significant increase of phosphor-AURKA/B/C, AURKA, AURKB, and PLK1, which fall into the mitotic kinase group.
View Article and Find Full Text PDFSci Rep
January 2025
Division of Medical Oncology, Marmara University School of Medicine, Istanbul, Turkey.
Management of melanoma has changed significantly with the discovery of targeted therapies and immune checkpoint inhibitors (ICI). Our aim in the study is to determine which treatment alternatives, specifically dabrafenib plus trametinib and ICIs, are effective in adjuvant therapy and which treatment is effective as first-line metastatic therapy. This retrospective, multicenter study included 120 patients diagnosed with stage IIIB-IIID melanoma receiving both adjuvant and first-line metastatic treatment between 2007 and 2023.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!