IMPDH2, or inosine monophosphate dehydrogenase 2, is a critical enzyme that catalyzes the first committed step in the de novo synthesis of guanine nucleotides, which are essential for DNA and RNA synthesis. It plays a significant role in cellular proliferation and the immune response. The protein is known to be upregulated in proliferating tissues and is associated with the development of some tumors, suggesting a role in malignant transformation. IMPDH2 has also been shown to interact with PARP1 on chromatin, modulating the DNA damage response by controlling PARP1 activity and nuclear NAD+ levels, which is crucial for cell survival and the balance of DNA damage repair. Additionally, IMPDH2 can reversibly polymerize in response to metabolic demands, and this self-assembly is recognized as a mechanism for regulating its activity, particularly by making the enzyme less sensitive to feedback inhibition under conditions that require an expansion of guanine nucleotide pools.
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