{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n AK3 has been implicated in a number of diverse biological contexts. In hematological malignancies, genomic deletions involving AK3 have been recurrently observed in relapsing high‐hyperdiploid acute lymphoblastic leukemia, suggesting a possible role for AK3 loss in disease evolution (from."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In breast cancer, studies have demonstrated that AK3 is directly targeted by microRNA‐96–5p; its downregulation is associated with enhanced MEK/ERK signaling, increased migratory capacity of tumor cells, and poorer overall survival, a finding that is further supported by its inclusion in a glycolysis‐related prognostic gene signature where its expression is uniquely decreased relative to other markers."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " In the setting of immune regulation, non‐coding genetic variants that impact AK3 expression have been associated with altered GM–CSF signaling in inflammatory bowel disease, implicating AK3 in the modulation of cytokine responsiveness in neutrophils."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its role in human disease, AK3 also serves distinct functions in lower eukaryotes and parasites. In Trypanosoma, a membrane‐associated protein designated as AK3 displays rapid, non‐polar turnover in flagella, contrasting with the stable incorporation of structural axonemal proteins; this dynamic behavior suggests that AK3 may be involved in regulating the composition or functionality of the flagellar membrane."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Similarly, in Clonorchis sinensis the adenylate kinase 3 homolog is expressed in the subtegumental tissue and secreted into the host’s bile duct, where its immunoreactivity makes it a promising candidate for serodiagnosis of clonorchiasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to its endogenous roles, “AK3” has been adopted as a designation for synthetic compounds that induce mitotic arrest and enhance apoptosis in cancer cells by elevating markers such as γH2AX and modulating TNF receptor expression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Finally, as a mitochondrial enzyme, AK3 localizes to the matrix where it reversibly catalyzes adenine nucleotide interconversion, thereby contributing to the balance between oxidative phosphorylation and glycolysis—an essential component of cellular energy homeostasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies indicate that AK3 functions both as a regulator of energy metabolism within mitochondria and as a modulator of cellular behavior in cancer and immune cells. The observations that diminished AK3 expression is linked to tumor aggressiveness and poor patient outcome, along with its diagnostic potential in parasitic infections and its utility as a target for pharmacological intervention, underscore its multifaceted roles in cellular physiology and disease."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_fs", "start_ref": "4", "end_ref": "8"}, {"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "J Davidsson, K Paulsson, D Lindgren, et al. 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