{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPericentriolar material 1 (PCM1) is a core scaffolding protein of centriolar satellites that orchestrates centrosomal organization and microtubule dynamics critical for cell cycle progression. For example, PCM1 localizes to dynamic cytoplasmic granules and facilitates the recruitment of regulators such as Nek2, thereby promoting proper centrosomal function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In neural progenitors, PCM1 interacts with Hook3 to coordinate interkinetic nuclear migration"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ", and its association with CEP90 is essential for the accumulation of centriolar satellite proteins at the centrosome."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Furthermore, defects in centrosome duplication linked to NEK7-dependent processes underscore PCM1’s role in centrosome integrity"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ", while broader centrosomal dysfunction involving PCM1 has been implicated in the pathogenesis of major mental illnesses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nPCM1 is also pivotal for ciliogenesis. Its interaction with CEP290 helps promote the assembly of primary cilia"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ", and cooperation with wild-type Huntingtin further regulates ciliary vesicle trafficking to ensure proper cilium formation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " In addition, PCM1 facilitates ciliary disassembly by recruiting Polo-like kinase 1 (Plk1) to the pericentriolar matrix, enabling timely ciliary resorption before mitosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " By tethering the E3 ligase Mib1, PCM1 prevents premature degradation of key ciliary components, and its interaction with Hook2 further supports Rab8-dependent targeting during ciliogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nThe homeostasis of PCM1 is tightly regulated post‐translationally. The deubiquitylase USP9X directly associates with PCM1 to stabilize its levels"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": ", and its ability to antagonize PCM1 ubiquitylation is critical for preventing proteasomal degradation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": " Moreover, sorting nexin 17 (SNX17) recruits USP9X to centriolar satellites, a mechanism that is essential for maintaining PCM1 protein homeostasis under stress conditions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAlterations in PCM1 contribute to a spectrum of human diseases. Chromosomal rearrangements that generate PCM1‐JAK2 fusion proteins have been identified in various hematological malignancies—including atypical chronic myeloid leukemia"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": ", acute leukemias with immunophenotypic evolution"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": ", and T‐cell lymphomas."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "16"}]}, {"type": "t", "text": " In parallel, genetic variations in PCM1 have been linked to neuropsychiatric disorders such as schizophrenia; several studies report associations of PCM1 variants"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "18"}]}, {"type": "t", "text": ", DISC1‐mediated modulation of PCM1 localization"}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "19", "end_ref": "21"}]}, {"type": "t", "text": ", and neurodevelopmental defects upon PCM1 ablation"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "22"}]}, {"type": "t", "text": ", although some populations show no clear association."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "23"}]}, {"type": "t", "text": " Beyond neuropsychiatric conditions, a PCM1 3′ untranslated region variant has been associated with increased ovarian cancer risk"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "24"}]}, {"type": "t", "text": ", and recent work implicates long noncoding RNA interactions with PCM1 in modulating interferon‐γ responses in neurosyphilis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "25"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Rebecca S Hames, Renarta E Crookes, Kees R Straatman, et al. 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