{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPSME3IP1, also known as PIP30 or NIP30, acts as an important regulatory cofactor for the nuclear proteasome activator PA28γ. It directly binds to free or proteasome-associated PA28γ via a conserved C-terminal region whose interaction is reinforced by casein kinase 2 phosphorylation. This binding not only enhances the assembly of proteasome complexes but also modulates PA28γ‐dependent peptide degradation in an ATP‐ and ubiquitin-independent manner."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition, a phosphorylated isoform of PSME3IP1—referred to as NIP30—has been shown to function as an inhibitor of the oncogenic REGγ‐proteasome, thereby attenuating cell proliferation. Through an evolutionarily conserved serine‐rich domain, NIP30 regulates the degradation of key cell cycle regulators such as p21, a process modulated by CDC25A. This regulation is particularly crucial in p53‐deficient cells, where NIP30 sensitizes cancer cells to chemotherapeutic agents by modulating the activity of the REGγ proteasome."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nTogether, these findings highlight the dual role of PSME3IP1 in guiding proteasome function: by influencing both the assembly and substrate selectivity of PA28γ‐associated proteasomes and by impacting cell cycle progression and chemotherapeutic response in cancer contexts. The work underscores the emerging significance of small regulatory proteins in the fine‐tuning of proteasomal degradation and their potential as therapeutic targets in oncology.\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Beata Jonik-Nowak, Thomas Menneteau, Didier Fesquet, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PIP30/FAM192A is a novel regulator of the nuclear proteasome activator PA28γ."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1722299115"}], "href": "https://doi.org/10.1073/pnas.1722299115"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29934401"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29934401"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Xiao Gao, Qingwei Wang, Ying Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The REGγ inhibitor NIP30 increases sensitivity to chemotherapy in p53-deficient tumor cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-020-17667-7"}], "href": "https://doi.org/10.1038/s41467-020-17667-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32764536"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32764536"}]}]}]}