{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n ANKZF1 is emerging as a multifunctional factor that safeguards protein homeostasis through its critical roles in ribosome‐associated quality control (RQC) and as a p97/VCP‐interacting cofactor. In the context of translational quality control, ANKZF1 is recruited to stalled ribosome complexes where its endonuclease activity precisely cleaves the acceptor arm of peptidyl‐tRNA, thereby releasing ubiquitinated nascent chains from the 60S subunit. This cleavage, which eliminates the terminal 3′CCA nucleotides and generates a tRNA fragment that must later be repaired for re‐entry into translation, is a key step that facilitates proteasomal degradation of aberrant peptides and prevents the accumulation of potentially toxic intermediates (1,4,5,6). In parallel, ANKZF1 binds to the p97/VCP ATPase through a VCP‐interacting motif (VIM) that has been defined by a minimal consensus sequence, positioning it among a novel family of cofactors that modulate p97 function and, thereby, influence diverse cellular processes including protein degradation and stress responses (2,3). \n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Furthermore, altered expression or mutation of ANKZF1 has been linked to various human diseases. Gene expression profiling and prognostic modeling in several cancers—including colon adenocarcinoma, renal cell carcinoma, clear cell renal cell carcinoma, hepatocellular carcinoma, rectal cancer, and prostate cancer—have identified ANKZF1 as a component of glycolysis‐related risk signatures, suggesting that its dysregulation may impact not only protein quality control but also metabolic pathways that contribute to tumor progression (7,8,9,10,11,12). In addition, rare mutations in ANKZF1 have been detected in patients with infantile‐onset inflammatory bowel disease, underscoring its physiological relevance in human health (13).\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings indicate that ANKZF1 functions both as an essential RQC factor—ensuring the fidelity of translation by liberating aberrant nascent chains from stalled ribosomes—and as a high‐affinity p97/VCP cofactor that may influence downstream processes related to protein turnover and cellular metabolism.\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n "}, {"type": "b", "children": [{"type": "t", "text": "Citations:"}]}, {"type": "t", "text": "<br>\n (1)"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ", \n (2)"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ", \n (3)"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ", \n (4)"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ", \n (5)"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ", \n (6)"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ", \n (7)"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ", \n (8)"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ", \n (9)"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": ", \n (10)"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": ", \n (11)"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": ", \n (12)"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": ", \n (13)."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Kazushige Kuroha, Alexandra Zinoviev, Christopher U T Hellen, et al. 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