Human IMP dehydrogenase (E.C. 1.1.1.205) is recently regarded as a potent targeting enzyme for immunosuppressive drugs. Tissue differential expressions of human type I and type II IMP dehydrogenase were investigated in sixteen human adult organs (heart, brain, placenta, lung, liver, skeletal muscle, kidney, pancreas, spleen, thymus, prostate, testis, ovary, small intestine, colon, peripheral blood leukocytes) and five human fetal organs (heart, brain, lung, liver, kidney) using Northern blot analysis. In all tissues examined in this study, the sizes of mRNAs of each isoform were identical, respectively. The 2.3 kb type II mRNA was shown predominantly, and the 3.5 kb type I mRNA level was lower than type II in most human tissues examined. In contrast, type I IMPDH gene expressed higher than type II in peripheral blood leukocytes, uniquely. We also demonstrated that both type I and type II IMPDH genes are widely distributed among various species by Southern blot analysis. Interestingly, type I IMPDH gene may have multiple gene families in primates.
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http://dx.doi.org/10.1016/0024-3205(94)90150-3 | DOI Listing |
ACS Infect Dis
January 2025
Department of Chemistry, Brandeis University, Waltham, Massachusetts 02454, United States.
Inosine 5'-monophosphate dehydrogenase (IMPDH) is a promising antibiotic target. This enzyme catalyzes the NAD-dependent oxidation of inosine 5'-monophosphate (IMP) to xanthosine 5'-monophosphate (XMP), which is the rate-limiting step in guanine nucleotide biosynthesis. Bacterial IMPDH-specific inhibitors have been developed that bind to the NAD site.
View Article and Find Full Text PDFBiochemistry (Mosc)
December 2024
Institute of Biochemistry and Biophysics, University of Tehran, Tehran, 13145-1384, Iran.
Inosine Monophosphate Dehydrogenase (IMPDH) catalyzes rate-limiting step of the reaction converting inosine monophosphate (IMP) to guanine nucleotides. IMPDH is up-regulated in the healthy proliferating cells and also in tumor cells to meet their elevated demand for guanine nucleotides. An exclusive regulatory mechanism for this enzyme is filamentation, through which IMPDH can resist allosteric inhibition by the end product, GTP.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Centre for Tuberculosis Research, Tuberculosis Research Laboratory, Translational Health Science and Technology Institute, National Capital Region Biotech Science Cluster 3rd Milestone, Faridabad, Haryana 121001, India.
Itaconate, an abundant metabolite produced by macrophages upon interferon-γ stimulation, possesses both antibacterial and immunomodulatory properties. Despite its crucial role in immunity and antimicrobial control, its mechanism of action and dissimilation are poorly understood. Here, we demonstrate that infection of mice with increases itaconate levels in lung tissues.
View Article and Find Full Text PDFSci Rep
January 2025
Department of Cell Stress Biology, Roswell Park Comprehensive Cancer Center, CGP L3-317, Buffalo, NY, 14263, USA.
Triple negative breast cancer (TNBC) is one of the deadliest subtypes of breast cancer, whose high frequency of relapse is often due to resistance to chemotherapy. Here, we identify inosine monophosphate dehydrogenase 2 (IMPDH2) as a contributor to doxorubicin resistance, in multiple TNBC models. Analysis of publicly available datasets reveals elevated IMPDH2 expression to associate with worse overall TNBC prognosis in the clinic, including lower recurrence-free survival post adjuvant/neoadjuvant therapy.
View Article and Find Full Text PDFCell Rep
December 2024
Department of Liver Surgery and Shanghai Cancer Institute, State Key Laboratory of Systems Medicine for Cancer, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, School of Pharmacy, East China University of Science and Technology, Shanghai, China. Electronic address:
Inosine monophosphate dehydrogenase 2 (IMPDH2) is highly expressed in human cancers; however, its physiological relevance under growth signaling remains to be investigated. Here, we show that IMPDH2 serine 122 is phosphorylated by CDK1, and this modification attenuates the catalytic activity of IMPDH2 for IMP oxidation and simultaneously represses its allosteric modulation by purine nucleotides. Fibroblast growth factor receptor (FGFR) signaling activation triggers IMPDH2-Ser122 dephosphorylation mediated by protein phosphatase 2A (PP2A), which is dependent on FGFR3-mediated PPP2R1A-Tyr261 phosphorylation leading to PPP2CA-PPP2R1A-IMPDH2 interactions.
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