PLK1 (P53350) curation notes

Identity and architecture

• Human Polo-like kinase 1, 603 aa; N-terminal Ser/Thr kinase domain (~39-325) and C-terminal tandem polo-box domain (PBD, ~365-603) that binds Ser-[pThr/pSer]-Pro/X motifs (UniProt DOMAIN comment; deep research, Wyatt & McInnes 2024 model).
• Activation: Aurora A/BORA phosphorylate Thr210 in late G2 PMID:18615013. Thr210 is the major activating site; Ser137 is not detectably phosphorylated in mitotic cells PMID:12207013. MYPT1-PP1 antagonizes Thr210 phosphorylation PMID:18477460.
• Kinase-domain structure with AMPPNP and PHA-680626 PMID:17461553; PBD crystal structures with CDC25C and PBIP1-derived phosphopeptides [PMID:17307877; PMID:19597481].

Core functions (basis for core_functions)

1. Mitotic entry (G2/M transition). CDC25C phosphorylation/activation PMID:11202906; WEE1 S53 phosphorylation creating the beta-TrCP degron PMID:15070733; cyclin B1 phosphorylation on centrosomes in prophase PMID:12524548; FOXM1 activation after CDK1 priming PMID:19160488; NEBD via p150Glued S179 PMID:20679239. Reactome: Activation of Cdc25C, Inactivation of Wee1, Inactivation of Myt1.
2. Centrosome maturation / bipolar spindle. Antibody microinjection blocks functional maturation of mitotic centrosomes PMID:8991084; gamma-tubulin recruitment requires PLK1 PMID:18477460; Kizuna phosphorylation stabilizes spindle poles PMID:16980960; MST2 phosphorylation licenses NEK2A-driven centrosome disjunction PMID:21723128; NEK9 activation -> EG5 PMID:21642957; BORA turnover controls Aurora A localization PMID:18521620; PRC1 T602 phosphorylation prevents premature midzone formation PMID:22621898.
3. Kinetochore / segregation / APC/C activation. Kinetochore docking on CDK1-phosphorylated BUB1 T609 PMID:16760428; SGO1-dependent kinetochore binding PMID:17617734; CENP-Q/U complex targets PLK1 to kinetochores PMID:25395579; CUL3-KLHL22 removes PLK1 from kinetochores for SAC satisfaction PMID:23455478; EMI1 degron phosphorylation -> APC/C activation PMID:15148369; CDC6 T37 -> separase release PMID:21041660. Cohesin removal by SA2 phosphorylation (Reactome R-HSA-1638803 / R-HSA-2466068).
4. Cytokinesis. Self-targeting to midzone via MKlp2 and PRC1 docking [PMID:12939256; PMID:17351640]; RACGAP1/HsCYK-4 S157 phosphorylation creates the ECT2 BRCT docking site required for furrowing [PMID:19468302; PMID:19468300 "Failure to phosphorylate HsCyk-4 blocks Ect2 recruitment to the central spindle and the subsequent induction of furrowing"]; midbody localization [PMID:30715179; PMID:41361016].

Non-core / secondary roles (KEEP_AS_NON_CORE)

• DNA damage checkpoint recovery: CLASPIN degron PMID:16885022, WEE1, 53BP1/CHK2 PMID:20126263, MRE11 S649 PMID:28512243. PLK1 is degraded by APC/C-CDH1 to allow the G2 checkpoint PMID:18662541 -- it opposes the checkpoint, hence MODIFY of GO:0007095 to negative regulation of DNA damage checkpoint (GO:2000002).
• DSB repair: RAD51 S14 PMID:22325354; mitotic MMEJ via RHNO1 PMID:37440612 and POLQ PMID:37674080.
• p53/p73 axis: TOPORS S718 PMID:19473992, MDM2 S260 PMID:19833129, GTSE1 S435 PMID:20577264, p73 T27 PMID:18174154. Treated as over-annotation for the apoptosis/transcription process terms, consistent with the CDK1 review.
• Golgi (GORASP1), cilia (DVL2, NPHP1), meiotic SC disassembly (mouse, PMID:22854038).

Curation decisions worth flagging

• GO:0005515 protein binding (91 IPI rows): REMOVE as uninformative except where the paper demonstrates phospho-dependent PBD docking, which was MODIFIED to GO:0051219 phosphoprotein binding (MKlp2, BUB1, CDC25C, TTDN1, PRC1, HBO1, MYPT1, FOXM1, PBIP1/CDC25C peptides, DVL2).
• GO:0007062 sister chromatid cohesion (Reactome TAS x2): MODIFY to GO:0045875 negative regulation of sister chromatid cohesion; PLK1 phosphorylation of SA2 removes cohesin.
• GO:0007095 G2 DNA damage checkpoint signaling: MODIFY to GO:2000002 (see above).
• GO:0007346 regulation of mitotic cell cycle (CYLD paper): MODIFY to GO:0010971 positive regulation of G2/M transition.
• GO:0045184 establishment of protein localization: MODIFY to GO:0071539 protein localization to centrosome (sSgo1 spindle-pole localization).
• GO:0004672 protein kinase activity: MODIFY to GO:0004674 (Ser/Thr specificity established).
• GO:0019901 protein kinase binding (STK10, AURKA) and GO:0042802 identical protein binding (x3): REMOVE as uninformative binding terms; PLK1 is the substrate of both kinases.
• GO:0010997 APC/C binding: MARK_AS_OVER_ANNOTATED; derived from PLK1 being an APC/C-CDH1 substrate.
• UNDECIDED: GO:0034451 centriolar satellite (IEA from mouse; source not examinable) and GO:0071168 protein localization to chromatin (PMID:21111234 cache is abstract-only and does not mention PLK1).
• No NEW terms proposed; the existing set already covers the core functions.

Reference caveats

• PMID:23354166 is a Drosophila study; PMID:20534861 is HCV NS5A phosphorylation; PMID:18195732 abstract is about cyclin B1 (PLK1 outer-kinetochore localization presumably in full text); PMID:21111234 cached record does not mention PLK1.
• Abstract-only caches: 46 of 93 PMIDs; where the abstract does not show the relevant data the curator's full-text reading was deferred to (ACCEPT), per repository rules.