Targeting AURKA in Cancer: molecular mechanisms and opportunities for Cancer therapy

Du, Ruijuan; Huang, Chuntian; Liu, Kangdong; Li, Xiang; Dong, Zigang

doi:10.1186/s12943-020-01305-3

Molecular Cancer

Table 1 Upstream molecules that regulate AURKA

From: Targeting AURKA in Cancer: molecular mechanisms and opportunities for Cancer therapy

Positive regulators of AURKA
Names	Functions	Mechanisms	Ref
FOXM1	Activates AURKA expression at the transcriptional level	FOXM1 binds directly to AURKA promoter to activate AURKA expression.	[1]
ARID3A	Promotes AURKA transcription	Binds to AURKA promoter.	[2]
PUF60	Promotes AURKA transcription	Binds to AURKA promoter.	[3]
E4TF1	Promotes AURKA transcription	Binds to positive regulatory element of AURKA promoter.	[4]
TRAP220/MED1	Promotes AURKA transcription	It binds between the transcription machinery and the GABPα subunit at a region between − 169 and − 98 of AURKA promoter.	[5]
EGFR/ STAT5	Promotes AURKA transcription	EGF induces recruitment of nuclear EGFR and STAT5 to the AURKA promoter.	[6]
β-catenin/ TCF4	Promotes AURKA transcription	Binds to AURKA promoter and enhances AURKA promoter activity.	[7]
HnRNPQ1	Increases the translational efficiency of AURKA mRNA	Enhances the recruitment of ribosomes to those regions of AURKA 5 ′-UTRs.	[8]
NEDD9	Stabilizes AURKA protein expression and increases AURKA activity	Protects AURKA from binding cdh1; Stimulates AURKA autophosphorylation at Thr288.	[9]
TPX2	Ehances AURKA stability and activity	Interaction between AURKA and TPX2 and disassociation from cdh1 is required for protecting AURKA from degradation; Stimulates autophosphorylation and autoactivation of AURKA.	[10, 11] [12]
PUM2	Promotes AURKA stability and activity	Protects AURKA from cdh1-mediated degradation; Increases p-Histone-H3 levels.	[13]
LIMK2	Inhibits AURKA degradation	Association of LIM domains with AURKA is sufficient for AURKA stabilization.	[14]
Twist	Inhibits AURKA degradation	Ubiquitin-proteosomal degradation pathway.	[15]
ALDH1A1	Inhibits AURKA degradation	Ubiquitin-proteosomal degradation pathway.	[16]
YBX1	Inhibits AURKA degradation	Ubiquitin -proteosomal degradation pathway.	[17]
USP2a	Inhibits AURKA degradation	Removes ubiquitin from AURKA.	[18]
PKC	Increases AURKA activity	Phosphorylates AURKA at Thr287, which augments interaction with TPX2.	[19]
PNUTS	Increases AURKA activity	Blocks PP1-dependent dephosphorylation of AURKA.	[20]
BuGZ	Increases AURKA activity	Zinc figers in BuGZ directly bind to the kinase domain of AURKA and stimulates autophosphorylation at Thr288.	[21]
RASSF1A	Increases AURKA activity	Stimulates AURKA autophosphorylation at Thr288.	[22]
IPP2	Increases AURKA activity	Ability to activate MBP is enhanced through inhibition of PP1. No increase in p-Thr288.	[23]
PAK1	Increases AURKA activity	Phosphorylates AURKA at Thr288 and Ser342 sites in the activation loop.	[24]
Ajuba	Increases AURKA activity	Stimulates AURKA autophosphorylation at Thr288 and kinase activity toward histone H3.	[25]
KCTD12	Increases AURKA activity	Stimulates AURKA autophosphorylation at Thr288.	[26]
Negative regulators of AURKA
Names	Functions	Mechanisms	Ref
INI1/hSNF5	Represses AURKA transcription	Associates with AURKA promoter.	[27]
ARID1A	Represses AURKA transcription	Associates with AURKA promoter.	[28]
SIX3	Represses AURKA transcription	Associates with AURKA promoter.	[29]
MCPIP1	Inhibits AURKA transcription	Destabilizes AURKA mRNA	[30]
Cdh1	Induces AURKA degradation	Cdh1-APC/C-ubiquitin-proteasome pathway.	[31]
NQO1	Induces AURKA degradation	NQO1 competes with TPX2 for binding to AURKA.	[32]
SMAD4	Induces AURKA degradation	Ubiquitin -proteosomal degradation pathway.	[33]
RPL3	Induces AURKA degradation	Depends on PRL-3-mediated dephosphorylation of FZR1 and assembly of the APC/C^FZR1 complex.	[34]
IKK2	Induces AURKA degradation	IKK2 phosphorylation of AURKA targets it for β-TRCP-mediated proteasomal degradation.	[35]
AURKAIP1	Induces AURKA degradation	Interaction with AURKA is essential for degradation.	[36] [37]
VHL	Induces AURKA degradation	VHL recognition of AURKA occurs independent of prolyl hydroxylation and results in multi-monoubiquitination.	[38]
PTPRD	Induces AURKA degradation	Dephosphorylates tyrosine residues in AURKA.	[39]
PHLDA1	Induces AURKA degradation	Ubiquitin-proteosomal degradation pathway.	[40]
PTTG1	Inhibits AURKA activity	Attenuates AURKA autophosphorylation at Thr288 and p-Histone-H3 level.	[41]
Gadd45a	Inhibits AURKA activity	Attenuates AURKA ability to phosphorylate MBP.	[42]
PP1	Inhibits AURKA activity	Dephosphorylates AURKA and abolishes kinase activity.	[43]
GSK-3β	Inhibits AURKA activity	Phosphorylates AURKA on S290/291, leading to autophosphorylation of serine 349.	[44]

Multiple myeloma SET domain protein (MMSET); Forkhead box subclass M1 (FOXM1); Human Pumilio homology protein 2 (PUM2); LIM-domain kinase-2 (LIMK2); Aldehyde dehydrogenase 1 (ALDH1A1); Y-box binding protein-1 (YBX1); Protein kinase C (PKC); Phosphatase 1 nuclear targeting subunit (PNUTS); RAS-association domain family 1, isoform A (RASSF1A); Protein phosphatase inhibitor-2(IPP2); P21-activated kinase 1 (PAK1); Potassium channel tetramerization domain containing 12 (KCTD12); Nicotinamide adenine dinucleotide(P) H quinone oxidoreductase 1 (NQO1); Phosphatase of Regenerating Liver-3 (RPL3); IκB kinase 2 (IKK2); Aurora-A Kinase interacting protein (AURKAIP1); Von Hippel-Lindau (VHL); Protein tyrosine phosphatase receptor delta (PTPRD); Pleckstrin homology-like domain family A member 1(PHLDA1); Pituitary tumor transforming gene 1 (PTTG1); Protein Phosphatase 1 (PP1); Glycogen synthase kinase 3 beta (GSK-3β); monocyte chemoattractant protein-induced protein 1 (MCPIP1); poly(U) binding splicing factor 60 (PUF60); SIX homeobox 3 (SIX3); AT-rich interactive domain 1A (ARID1A); AT-rich interaction domain 3A (ARID3A)

Back to article page

ISSN: 1476-4598

Contact us

General enquiries: journalsubmissions@springernature.com