IMPDH2 catalyzes the conversion of inosine 5'-monophosphate (IMP) to xanthosine 5'-monophosphate (XMP), the rate-limiting step in de novo guanine nucleotide synthesis . This enzyme is upregulated in proliferating cells and malignancies, making it a biomarker for cancer aggressiveness and a therapeutic target . IMPDH2’s nuclear localization has recently been linked to PARP1-mediated DNA repair via NAD+ modulation .
IMPDH2 antibodies are widely used in:
Western blotting (WB): Detects endogenous IMPDH2 at ~55–56 kDa .
Immunoprecipitation (IP): Identifies protein interactions, such as IMPDH2’s association with anti-apoptotic pathways .
Immunohistochemistry (IHC): Highlights IMPDH2 overexpression in hepatocellular carcinoma (HCC) and nasopharyngeal carcinoma (NPC) .
Immunofluorescence (IF): Visualizes IMPDH2 clustering into cytoophidia (rod/ring structures) under nucleotide stress .
Triple-negative breast cancer (TNBC): IMPDH2 overexpression correlates with doxorubicin resistance and poor recurrence-free survival. Pharmacological inhibition (e.g., mycophenolic acid) reduces tumor growth in vitro and in vivo .
Mechanistic insights: IMPDH2 knockdown decreases intracellular GTP levels by 20–50%, impairing survival pathways in resistant cells . Catalytically inactive IMPDH2 mutants fail to restore chemoresistance, confirming its enzymatic dependency .
PARP1 interaction: Nuclear IMPDH2 modulates NAD+ availability, enhancing PARP1 activity during DNA damage response. TNBC tissues show elevated nuclear IMPDH2, linking it to genomic instability .
Specificity: Antibodies like MAB8349 show no cross-reactivity with IMPDH1 despite 84% amino acid similarity .
Functional assays: Microinjection of anti-IMPDH2 antibodies disassembles cytoophidia in COS-7 cells, confirming target engagement .
Clinical relevance: IHC-validated IMPDH2 antibodies correlate staining intensity with tumor grade and patient outcomes .