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Table 2 AURKA downstream substrates

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

Substrates

Phosphorylation sites

Experimental methods

Functional significance

Ref

YBX1

T62, S102

Consensus motif, in vitro kinase assay, autoradiography

Increases YBX1 protein stability, regulate EMT, CSC and chemoresistance.

[17]

LDHB

S162

In vitro kinase assay, MS analysis, point mutation, anti-phosphoserine

Promotes glycolysis and biosynthesis; Promotes tumor growth.

[45]

Merlin

S518

In vitro kinase assay, specifc antibody

Weakens merlin interaction with tubulin.

[46]

RPS6KB1

T389

P-RPS6KB1 (T389) specifc antibody

Reduces survival of KRAS-mutant gastrointestinal cancer cells

[47]

CENP-A

S7

In vitro kinase assay, truncation mutants, autoradiography

Regulates mitosis especially kinetochore function.

[48]

LKB1

S299

In vitro kinase assay, MS analysis,

point mutation, autoradiography

Impairs LKB1 interaction with and phosphorylation of AMPK.

[49]

KCTD12

S243

Point mutation, IP, anti-phosphoserine

Promotion of cancer cell proliferation and tumorigenesis.

[26]

CHIP

S273

Point mutation, in vitro kinase assay, autoradiography

Promotes AR degradation via the proteasome pathway.

[50]

ALDH1A1

T267, T442, T493

Consensus motif, point mutation, in vitro kinase assay, autoradiography

Regulates protein stability, EMT and CSC phenotypes.

[16]

Twist

S123, T148,

S184

Consensus motif, point mutation, in vitro kinase assay, autoradiography

Regulates protein stability, subcellular localization, EMT, the CSC phenotype and drug resistance.

[15]

YAP

S397

In vitro kinase assay, truncation mutants, MS, consensus motif

Enhances transforming ability.

[51]

TACC3

S558

MS, point mutation, in vitro kinase assay, autoradiography

Regulates TACC3 localization to centrosomes and proximal mitotic spindles.

[52]

HDM2

S166

In vitro kinase assay, specifc antibody

NA

[53]

β-catenin

S552,

S675

In vitro kinase assay, truncation mutants, autoradiography

Increases its stability and transcriptional activity

[54]

ERα

S167,

S305

In vitro kinase assay, truncation mutants, autoradiography

Leading to increase in ERα DNA-binding and transcriptional activity.

[55]

BimEL

S93/94/98

Consensus motif, in vitro kinase assay, specifc antibody

NA

[56]

GSK-3β

S9

In vitro kinase assay, specifc antibody

Leading to accumulation and activation of the β-catenin/TCF complex.

[57]

PLK1

T210

In vitro kinase assay, specifc antibody

Centrosomal organization.

[58]

IκBα

S32, S36

Specifc antibody

NFκB activation.

[59]

VHL

S72

In vitro kinase assay, MS, autoradiography

NA

[60]

PHLDA1

S98

In vitro kinase assay, consensus motif, autoradiography

Negatively regulates PHLDA1 by promoting PHLDA1 degradation.

[40]

Histone H3

S10

In vitro kinase assay, autoradiography

Involved in the initiation of mitosis.

[61]

YY1

S365

In vitro kinase assay, truncation mutants, consensus motif, autoradiography

Abolishes its DNA binding activity and transcriptional activity.

[62]

SDCBP

S131,

T200

In vitro kinase assay, consensus motif, autoradiography, anti-phospho-serine/threonine

Stabilizes SDCBP protein and regulates its oncogenic function.

[63]

SOX2

S220, S251

In vitro kinase assay, MS

Maintains the ratio of stem-cell like cells.

[64]

CPAP

S467

In vitro kinase assay, truncation mutants, MS, autoradiography

Is required for the integrity of the spindle pole during mitosis.

[65]

RalA

S194

In vitro kinase assay, consensus motif, autoradiography

Enhances cell migration and anchorage-independent growth.

[66]

CDC25B

S353

MS, in vitro kinase assay, specifc antibody

Control of the onset of mitosis.

[67]

NDEL1

S251

MS, in vitro kinase assay, autoradiography

Centrosomal maturation, separation, and TACC3 recruitment.

[68]

ASAP

S625

MS, in vitro kinase assay, autoradiography

Bipolar spindle assembly.

[69]

MBD3

S24

In vitro kinase assay, autoradiography, consensus motif

NA

[70]

RASSF1A

T202, S203

Consensus motif, in vitro kinase assay, autoradiography

Induces M-phase cell cycle arrest.

[71]

P53

S215,

S315

S106

Consensus motif, in vitro kinase assay, autoradiography

S215: Abrogates DNA binding and transactivation activity;

S315: Inactivates p53 by enhancing its proteolytic degradation.

S106: Inhibit the interaction of p53 with MDM2 and prolong the half-life of p53.

[72] [73]

[74]

HURP

S627, S725,

S757, S830

In vitro kinase assay,autoradiography, MS

Regulates HURP stability and exhibits serum-independent growth.

[75]

PP1

NA

In vitro kinase assay,autoradiography

Inhibits PP1 activity at mitosis.

[43]

P73

S235

Consensus motif, in vitro kinase assay, autoradiography

Abrogates its transactivation function; Regulates subcellular localization.

[76]

TPX2

S121,

S125

Consensus motif, in vitro kinase assay, autoradiography

Maintains metaphase spindle length by regulating the microtubules flux.

[77]

Lats2

S83

In vitro kinase assay, truncation mutants, autoradiography

Regulates centrosomal localization.

[78]

LIMK2

S283, T494,

T505

Consensus motif, in vitro kinase assay, autoradiography

Inhibits LIMK2 degradation and increases LIMK2 kinase activity.

[14]

  1. Y-box binding protein-1 (YBX1); Lactate dehydrogenase B (LDHB); Ribosomal protein S6 kinase B1 (RPS6KB1); Centromeric protein A (CENP-A); Liver kinase B1 (LKB1); Potassium channel tetramerization domain containing 12 (KCTD12); C-terminus of HSP70-interacting protein (CHIP); Aldehyde dehydrogenase 1 (ALDH1A1); Yes-associated protein (YAP); Glycogen synthase kinase 3 beta (GSK-3β);Polo-like kinase-1 (PLK1); Pleckstrin homology-like domain family A member 1(PHLDA1); Yin Yang 1 (YY1); Syndecan binding protein (SDCBP); Sex-determining region Y (SRY)-Box 2 (SOX2); Centrosomal P4.1-associated protein (CPAP); Ral small GTPase (RalA); Neurodevelopment protein 1-like 1 (NDEL1); ASter-Associated Protein (ASAP); RAS-association domain family 1, isoform A (RASSF1A); Hepatoma upregulated protein (HURP); Protein Phosphatase 1 (PP1); Large tumor suppressor 2 (Lats2); LIM-domain kinase-2 (LIMK2); Mass spectrometry (MS); NA: not available