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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/CFZR1 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]
  1. 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)