PLK1

Gene Information

Official Symbol: PLK1
Official Name: polo like kinase 1
Aliases and Previous Symbols: N/A
Entrez ID: 5347
UniProt: P53350
Interactions: BioGRID
PubMed articles: Open PubMed
OMIM: Open OMIM

Function Summary

Entrez Summary: N/A
UniProt Summary: Serine/threonine-protein kinase that performs several important functions throughout M phase of the cell cycle, including the regulation of centrosome maturation and spindle assembly, the removal of cohesins from chromosome arms, the inactivation of anaphase-promoting complex/cyclosome (APC/C) inhibitors, and the regulation of mitotic exit and cytokinesis. Polo-like kinase proteins acts by binding and phosphorylating proteins are that already phosphorylated on a specific motif recognized by the POLO box domains. Phosphorylates BORA, BUB1B/BUBR1, CCNB1, CDC25C, CEP55, ECT2, ERCC6L, FBXO5/EMI1, FOXM1, KIF20A/MKLP2, CENPU, NEDD1, NINL, NPM1, NUDC, PKMYT1/MYT1, KIZ, PPP1R12A/MYPT1, PRC1, RACGAP1/CYK4, SGO1, STAG2/SA2, TEX14, TOPORS, p73/TP73, TPT1, WEE1 and HNRNPU. Plays a key role in centrosome functions and the assembly of bipolar spindles by phosphorylating KIZ, NEDD1 and NINL. NEDD1 phosphorylation promotes subsequent targeting of the gamma-tubulin ring complex (gTuRC) to the centrosome, an important step for spindle formation. Phosphorylation of NINL component of the centrosome leads to NINL dissociation from other centrosomal proteins. Involved in mitosis exit and cytokinesis by phosphorylating CEP55, ECT2, KIF20A/MKLP2, CENPU, PRC1 and RACGAP1. Recruited at the central spindle by phosphorylating and docking PRC1 and KIF20A/MKLP2; creates its own docking sites on PRC1 and KIF20A/MKLP2 by mediating phosphorylation of sites subsequently recognized by the POLO box domains. Phosphorylates RACGAP1, thereby creating a docking site for the Rho GTP exchange factor ECT2 that is essential for the cleavage furrow formation. Promotes the central spindle recruitment of ECT2. Plays a central role in G2/M transition of mitotic cell cycle by phosphorylating CCNB1, CDC25C, FOXM1, CENPU, PKMYT1/MYT1, PPP1R12A/MYPT1 and WEE1. Part of a regulatory circuit that promotes the activation of CDK1 by phosphorylating the positive regulator CDC25C and inhibiting the negative regulators WEE1 and PKMYT1/MYT1. Also acts by mediating phosphorylation of cyclin-B1 (CCNB1) on centrosomes in prophase. Phosphorylates FOXM1, a key mitotic transcription regulator, leading to enhance FOXM1 transcriptional activity. Involved in kinetochore functions and sister chromatid cohesion by phosphorylating BUB1B/BUBR1, FBXO5/EMI1 and STAG2/SA2. PLK1 is high on non-attached kinetochores suggesting a role of PLK1 in kinetochore attachment or in spindle assembly checkpoint (SAC) regulation. Required for kinetochore localization of BUB1B. Regulates the dissociation of cohesin from chromosomes by phosphorylating cohesin subunits such as STAG2/SA2. Phosphorylates SGO1: required for spindle pole localization of isoform 3 of SGO1 and plays a role in regulating its centriole cohesion function. Mediates phosphorylation of FBXO5/EMI1, a negative regulator of the APC/C complex during prophase, leading to FBXO5/EMI1 ubiquitination and degradation by the proteasome. Acts as a negative regulator of p53 family members: phosphorylates TOPORS, leading to inhibit the sumoylation of p53/TP53 and simultaneously enhance the ubiquitination and subsequent degradation of p53/TP53. Phosphorylates the transactivation domain of the transcription factor p73/TP73, leading to inhibit p73/TP73-mediated transcriptional activation and pro-apoptotic functions. Phosphorylates BORA, and thereby promotes the degradation of BORA. Contributes to the regulation of AURKA function. Also required for recovery after DNA damage checkpoint and entry into mitosis. Phosphorylates MISP, leading to stabilization of cortical and astral microtubule attachments required for proper spindle positioning (PubMed:8991084, PubMed:11202906, PubMed:12207013, PubMed:12447691, PubMed:12524548, PubMed:12738781, PubMed:12852856, PubMed:12939256, PubMed:14532005, PubMed:14734534, PubMed:15070733, PubMed:15148369, PubMed:15469984, PubMed:16198290, PubMed:16247472, PubMed:16980960, PubMed:17081991, PubMed:17351640, PubMed:17376779, PubMed:17617734, PubMed:18174154, PubMed:18331714, PubMed:18418051, PubMed:18477460, PubMed:18521620, PubMed:18615013, PubMed:19160488, PubMed:19351716, PubMed:19468300, PubMed:19468302, PubMed:19473992, PubMed:19509060, PubMed:19597481, PubMed:23455478, PubMed:23509069). Together with MEIKIN, acts as a regulator of kinetochore function during meiosis I: required both for mono-orientation of kinetochores on sister chromosomes and protection of centromeric cohesin from separase-mediated cleavage (By similarity). Phosphorylates CEP68 and is required for its degradation (PubMed:25503564). Regulates nuclear envelope breakdown during prophase by phosphorylating DCTN1 resulting in its localization in the nuclear envelope (PubMed:20679239). Phosphorylates the heat shock transcription factor HSF1, promoting HSF1 nuclear translocation upon heat shock (PubMed:15661742). Phosphorylates HSF1 also in the early mitotic period; this phosphorylation regulates HSF1 localization to the spindle pole, the recruitment of the SCF(BTRC) ubiquitin ligase complex induicing HSF1 degradation, and hence mitotic progression (PubMed:18794143). Regulates mitotic progression by phosphorylating RIOK2 (PubMed:21880710). {ECO:0000250|UniProtKB:Q5F2C3, ECO:0000269|PubMed:11202906, ECO:0000269|PubMed:12207013, ECO:0000269|PubMed:12447691, ECO:0000269|PubMed:12524548, ECO:0000269|PubMed:12738781, ECO:0000269|PubMed:12852856, ECO:0000269|PubMed:12939256, ECO:0000269|PubMed:14532005, ECO:0000269|PubMed:14734534, ECO:0000269|PubMed:15070733, ECO:0000269|PubMed:15148369, ECO:0000269|PubMed:15469984, ECO:0000269|PubMed:15661742, ECO:0000269|PubMed:16198290, ECO:0000269|PubMed:16247472, ECO:0000269|PubMed:16980960, ECO:0000269|PubMed:17081991, ECO:0000269|PubMed:17351640, ECO:0000269|PubMed:17376779, ECO:0000269|PubMed:17617734, ECO:0000269|PubMed:18174154, ECO:0000269|PubMed:18331714, ECO:0000269|PubMed:18418051, ECO:0000269|PubMed:18477460, ECO:0000269|PubMed:18521620, ECO:0000269|PubMed:18615013, ECO:0000269|PubMed:18794143, ECO:0000269|PubMed:19160488, ECO:0000269|PubMed:19351716, ECO:0000269|PubMed:19468300, ECO:0000269|PubMed:19468302, ECO:0000269|PubMed:19473992, ECO:0000269|PubMed:19509060, ECO:0000269|PubMed:19597481, ECO:0000269|PubMed:20679239, ECO:0000269|PubMed:21880710, ECO:0000269|PubMed:23455478, ECO:0000269|PubMed:23509069, ECO:0000269|PubMed:25503564, ECO:0000269|PubMed:25986610, ECO:0000269|PubMed:8991084}.

Pfam Domains GO Terms

CRISPR Data

Compound Hit Most Correlated Genes in Chemogenomics Tissues where Essential in the Avana Dataset (DepMap 20Q1)

Screen	Score
iCRT14 30μM R08 exp492	-2.6
Ammonium tetrathiomolybdate 10μM R08 exp448	-2.39
GSK461364A 0.1μM R03 exp126	-2.07
Salinomycin 3.5μM R08 exp521	-2.07
BI-2536 0.0042μM R03 exp95	-2.02
BI-6727 0.04μM R03 exp98	-1.98
Vitamin-D3 40μM R08 exp536	-1.97
Oligomycin-A 20μM R00 exp26	-1.96
IU1-C 25μM R04 exp183	-1.84
Thimerosal 0.85μM R08 exp529	-1.75
Pimelic-diphenylamide-106 5μM R00 exp28	-1.74
Arsenate 40μM R06 exp264	-1.71
5-Fluorouracil 2μM R00 exp1	1.81
Cryptotanshinone 12μM R05 exp227	1.81
UM131593 0.1μM R01 exp58	1.82
YM155 0.0002μM R01 exp61	1.9
HMS-I1 1μM R01 exp46	2.02
UM0131023 0.05μM R05 exp248	2.07
Betulinic acid 10 to 15μM on day4 R05 exp222	2.09
CVT-10216 0.1μM R06 exp278	2.11
LLY-284 2.6μM R06 exp291	2.22
HMS-I2 1μM R06 exp286	2.3
Docetaxel 0.002μM R01 exp45	2.62
Taxol 0.002μM R01 exp54	3.05

Gene	Correlation
MT1E	0.52
PSMD3	0.501
POLR2J3	0.499
NUF2	0.496
TICRR	0.495
RAD21	0.493
TCEB3C	0.485
C14orf93	0.481
VASN	0.472
TCEB3CL2	0.472
PSMA6	0.471
DTL	0.469
KRT78	0.468
PSMB2	0.461
SUPT5H	0.456
CBWD3	0.455
AQR	0.452
NPIPB8	0.446
CLASP1	0.445
RBM39	0.444
NARFL	0.443
AAAS	0.443
PSMC1	0.443
TCEB3CL	0.441
RPL35	0.441
TBC1D3G	0.44
SYT9	0.44
GOLGA6L3	0.433
CBWD6	0.433
SLC4A1	0.432
NUP160	0.432
SSH2	0.432
HINFP	0.431
TBC1D3H	0.431
SUPT6H	0.429
ORC6	0.428
DHFR	0.427
RPS7	0.427
AHCTF1	0.426
ISCU	0.425
DOCK6	0.425
PSMB1	0.424
NUPL1	0.424
CLN6	0.424
HAUS4	0.422
HIST1H2BE	0.422
UQCRH	0.422
LRR1	0.422
UBL5	0.421
GPRIN2	0.419
EXOSC9	0.419
CDC73	0.418
POLR2A	0.418
SNRPA1	0.417
PAN3	0.416
MED15	0.416
MAT2A	0.416
C1QTNF9B	0.416
COL2A1	0.415
RPS2	0.415
DDTL	0.414
CACTIN	0.414
KRT2	0.413
TBC1D3F	0.413
SH3BP1	0.413
RAD51	0.412
GOLGA6L6	0.411
XAB2	0.411
CDC6	0.411
TTYH1	0.411
CBWD5	0.411
PSMD6	0.411
PSMA7	0.41
SCAF1	0.409
KPNB1	0.408
DNM2	0.408
RPSA	0.408
LRRC56	0.407
FAM231A	0.406
CDC45	0.405
IGFN1	0.405
FAM231C	0.405
NDC80	0.405
ATP6V0C	0.404
SEC13	0.404
GOLGA6L1	0.404
CHMP2A	0.404
SAP30BP	0.403
CHD4	0.403
FAM160A1	0.401
GOLGA6L4	0.401
OR10G3	0.4
BORA	0.4

Global Fraction of Cell Lines Where Essential: 723/726

Tissue	Fraction Of Cell Lines Where Essential
1290807.0	1/1
909776.0	1/1
bile duct	28/28
blood	28/28
bone	25/25
breast	33/33
central nervous system	56/56
cervix	4/4
colorectal	17/17
esophagus	13/13
fibroblast	1/1
gastric	15/15
kidney	20/21
liver	20/20
lung	75/75
lymphocyte	14/14
ovary	26/26
pancreas	24/24
peripheral nervous system	16/16
plasma cell	15/15
prostate	1/1
skin	24/24
soft tissue	7/7
thyroid	2/2
upper aerodigestive	22/22
urinary tract	29/29
uterus	4/5

Essentiality in NALM6

Essentiality Rank: 435
Expression level (log2 read counts): 7.1

Expression Distribution

Pkinase
Pkinase Tyr
POLO box

synaptonemal complex disassembly
condensed nuclear chromosome outer kinetochore
female meiosis chromosome segregation
regulation of protein localization to cell cortex
anaphase-promoting complex binding
protein localization to nuclear envelope
mitotic nuclear envelope disassembly
signal transduction involved in G2 DNA damage checkpoint
positive regulation of ubiquitin protein ligase activity
membrane disassembly
nuclear envelope disassembly
spindle checkpoint
spindle assembly checkpoint
regulation of mitotic spindle assembly
mitotic spindle checkpoint
mitotic spindle assembly checkpoint
regulation of ubiquitin protein ligase activity
synaptonemal complex organization
protein localization to chromatin
negative regulation of mitotic metaphase/anaphase transition
negative regulation of metaphase/anaphase transition of cell cycle
synaptonemal complex
spindle midzone
negative regulation of mitotic sister chromatid separation
negative regulation of chromosome separation
regulation of spindle assembly
establishment of mitotic spindle orientation
G2 DNA damage checkpoint
negative regulation of cyclin-dependent protein serine/threonine kinase activity
positive regulation of peptidyl-threonine phosphorylation
negative regulation of cyclin-dependent protein kinase activity
negative regulation of mitotic sister chromatid segregation
centriolar satellite
female meiotic nuclear division
negative regulation of sister chromatid segregation
positive regulation of ubiquitin-protein transferase activity
negative regulation of chromosome segregation
establishment of mitotic spindle localization
establishment of spindle orientation
spindle microtubule