IMPDH2 's Central Role in Cellular Growth and Diseases: A Potential Therapeutic Target

作者：Zheng Li, Yunpeng Zou, Jiayao Niu, Ying Zhang, Aohua Yang, Wenyu Lin, Jie Guo, Shuya Wang, Ronghan Liu · 发表于：Cell Proliferation · 年份：2025 · DOI：10.1111/cpr.70031 · 被引用次数：6 · 研究领域：Biochemical and Molecular Research、Adenosine and Purinergic Signaling、HIV/AIDS drug development and treatment

IMPDH2 is a rate-limiting enzyme in guanine nucleotide biosynthesis. It plays diverse roles in various physiological and pathological processes: nucleotide metabolism, inflammation, immune function, ribosomal stress. Structural or regulatory alterations in IMPDH2 are linked to significant health issues, and critical relevance in disease progression. We aim to underscore the potential of IMPDH2 as a promising therapeutic target for clinical applications. Inosine 5′-monophosphate dehydrogenase (IMPDH) is a rate-limiting enzyme in guanine nucleotide biosynthesis, catalysing the NAD+-dependent oxidation of inosine monophosphate (IMP) to xanthine monophosphate (XMP). IMPDH inhibition depletes the guanine nucleotide pool, reducing GTP levels and impairing cell proliferation, underscoring its critical role in DNA and RNA synthesis [1] (Figure 1). Two isoenzymes are present in human IMPDH, IMPDH1 and IMPDH2, a total of 514 amino acids, with 84% amino acid sequence similarity in amino acid sequence. The regulation of IMPDH activity is primarily mediated by IMPDH2, rather than IMPDH1 [3, 4]. IMPDH2, a prominent member of the IMPDH family, has gained the notable attention of researchers due to its diverse roles in cell proliferation, differentiation and chemoresistance [3]. IMPDH2 is universally expressed at the organ system level but has variable physiological expression levels within different tissues. Emerging research suggests that IMPDH2 has distinct functional roles in both physio...