AURKA

Oncogene
Aurora kinase A UniProt accession O14965

Mitotic serine/threonine kinase that contributes to the regulation of cell cycle progression (PubMed:11039908, PubMed:12390251, PubMed:17125279, PubMed:17360485, PubMed:18615013, PubMed:26246606). Associates with the centrosome and the spindle microtubules during mitosis and plays a critical role in various mitotic events including the establishment of mitotic spindle, centrosome duplication, centrosome separation as well as maturation, chromosomal alignment, spindle assembly checkpoint, and cytokinesis (PubMed:14523000, PubMed:26246606). Required for normal spindle positioning during mitosis and for the localization of NUMA1 and DCTN1 to the cell cortex during metaphase (PubMed:27335426).

Required for initial activation of CDK1 at centrosomes (PubMed:13678582, PubMed:15128871). Phosphorylates numerous target proteins, including ARHGEF2, BORA, BRCA1, CDC25B, DLGP5, HDAC6, KIF2A, LATS2, NDEL1, PARD3, PPP1R2, PLK1, RASSF1, TACC3, p53/TP53 and TPX2 (PubMed:11551964, PubMed:14702041, PubMed:15128871, PubMed:15147269, PubMed:15987997, PubMed:17604723, PubMed:18056443, PubMed:18615013). Phosphorylates MCRS1 which is required for MCRS1-mediated kinetochore fiber assembly and mitotic progression (PubMed:27192185).

Regulates KIF2A tubulin depolymerase activity (PubMed:19351716). Important for microtubule formation and/or stabilization (PubMed:18056443). Required for normal axon formation (PubMed:19812038).

Plays a role in microtubule remodeling during neurite extension (PubMed:19668197). Also acts as a key regulatory component of the p53/TP53 pathway, and particularly the checkpoint-response pathways critical for oncogenic transformation of cells, by phosphorylating and destabilizing p53/TP53 (PubMed:14702041). Phosphorylates its own inhibitors, the protein phosphatase type 1 (PP1) isoforms, to inhibit their activity (PubMed:11551964).

Inhibits cilia outgrowth (By similarity). Required for cilia disassembly via phosphorylation of HDAC6 and subsequent deacetylation of alpha-tubulin (PubMed:17604723, PubMed:20643351). Regulates protein levels of the anti-apoptosis protein BIRC5 by suppressing the expression of the SCF(FBXL7) E3 ubiquitin-protein ligase substrate adapter FBXL7 through the phosphorylation of the transcription factor FOXP1 (PubMed:28218735)

Source: UniProt

Part of a complex composed of NEDD9, AURKA and CTTN; within the complex NEDD9 acts as a scaffold protein and is required for complex formation (PubMed:24574519). Identified in a complex with AUNIP and NIN (PubMed:20596670). Interacts with FBXL7 (By similarity).

Interacts with CPEB1, JTB, TACC1, TPX2, PPP2CA, as well as with the protein phosphatase type 1 (PP1) isoforms PPP1CA, PPP1CB and PPP1CC (PubMed:11551964, PubMed:14580337, PubMed:14603251, PubMed:15966895, PubMed:17229885, PubMed:18662907, PubMed:19357306, PubMed:19668197, PubMed:19801554, PubMed:21225229, PubMed:27837025). Also interacts with its substrates ARHGEF2, BORA, KIF2A, PARD3, and p53/TP53 (PubMed:14702041, PubMed:16890155, PubMed:17488622, PubMed:19351716, PubMed:19812038). Interaction with BORA promotes phosphorylation of PLK1 (By similarity).

Interacts with CIMAP3 (PubMed:20643351). Interacts with GADD45A, competing with its oligomerization (PubMed:20460379). Interacts (via C-terminus) with AUNIP (via C-terminus) (PubMed:20596670).

Interacts with FRY; this interaction facilitates AURKA-mediated PLK1 phosphorylation (PubMed:22753416). Interacts with SIRT2 (PubMed:17726514, PubMed:22014574). Interacts with MYCN; interaction is phospho-independent and triggers AURKA activation; AURKA competes with FBXW7 for binding to unphosphorylated MYCN but not for binding to phosphorylated MYCN (PubMed:27837025).

Interacts with HNRNPU (PubMed:21242313, PubMed:25986610). Interacts with AAAS (PubMed:26246606). Interacts with KLHL18 and CUL3 (PubMed:23213400).

Interacts with FOXP1 (PubMed:28218735). Interacts with HDAC6; AURKA-mediated phosphorylation of HDAC6 promotes deacetylation of alpha-tubulin (PubMed:17604723)

Source: UniProt
Cytoplasm, cytoskeleton, microtubule organizing center, centrosome, Cytoplasm, cytoskeleton, spindle pole, Cytoplasm, cytoskeleton, microtubule organizing center, centrosome, centriole, Cell projection, neuron projection, Cell projection, cilium, Cytoplasm, cytoskeleton, cilium basal body, Basolateral cell membrane
Source: UniProt

Highly expressed in testis and weakly in skeletal muscle, thymus and spleen. Also highly expressed in colon, ovarian, prostate, neuroblastoma, breast and cervical cancer cell lines

Source: UniProt
  • APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1
  • Regulation of PLK1 Activity at G2/M Transition
  • SUMOylation of DNA replication proteins
  • TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest
  • Regulation of TP53 Activity through Phosphorylation
  • FBXL7 down-regulates AURKA during mitotic entry and in early mitosis
  • AURKA Activation by TPX2
  • Interaction between PHLDA1 and AURKA
Source: Reactome via UniProt

Mutations

Cancer Type Mutation Percentage
Central Nervous System Astrocytoma Grade Iv 0.09%
Lung Adenocarcinoma 0.17%
Lung Small Cell Carcinoma 0.59%
Lung Squamous Cell Carcinoma 0.27%
Oesophagus Adenocarcinoma 0.62%
Oesophagus Squamous Cell Carcinoma 0.82%
Pancreas Ductal Carcinoma 0.08%

Synthetic Lethal Network

Genes with an experimentally identified or computationally predicted synthetic-lethal relationship to AURKA, aggregated across our SSL data sources. Click any partner node to view that gene’s page.

Nodes and edges are coloured by the SSL data source. Partners appearing in more than one source are shown in grey.

BioGRID SLOrth SynLethDB MexDrugs Multi-source
Sources: BioGRID, SLOrth, SynLethDB, MexDrugs

Clinical Trials

Total Trials Found: 34

NCT ID Condition Brief Title Phase Status
NCT00500903 Advanced Malignancies A Study of MLN8237, a Novel Aurora A Kinase Inhibitor, in Participants With Advanced Solid Tumors PHASE1 COMPLETED
NCT02444884 Unspecified Childhood Solid Tumor, Excluding CNS, Neuroblastoma MLN8237 to Treat Children With Relapsed/Refractory Solid Tumors PHASE1 COMPLETED
NCT02327169 Advanced Nonhematologic Malignancies A Study MLN2480 in Combination With MLN0128 or Alisertib, or Paclitaxel, or Cetuximab, or Irinotecan in Adult Participants With Advanced Nonhematologic Malignancies PHASE1 COMPLETED
NCT00830518 Acute Myelogenous Leukemia, High-Grade Myelodysplastic Syndrome A Phase 2 Trial of MLN8237 in Adult Participants With Acute Myelogenous Leukemia and High-Grade Myelodysplastic Syndrome PHASE2 COMPLETED
NCT00697346 B-cell Follicular Lymphoma, B-cell Marginal Zone Lymphoma, Diffuse Large B-cell Lymphoma, B-cell Mantle Cell Lymphoma, B-cell Small Lymphocytic Lymphoma, B-Cell Chronic Lymphocytic Leukemia, Multiple Myeloma, Waldenstrom's Macroglobulinemia, Noncutaneous Peripheral T-cell Lymphoma Not Otherwise Specified, Angioimmunoblastic T-cell Lymphoma, Anaplastic Large Cell Lymphoma, Enteropathy Associated T-cell Lymphoma, NK Lymphoma Study of MLN8237 in Participants With Advanced Hematological Malignancies PHASE1 COMPLETED
NCT01045421 Advanced Nonhematological Malignancies, Non-Small Cell Lung Cancer, Small Cell Lung Cancer, Metastatic Breast Cancer, Head and Neck Squamous Cell Carcinoma, Gastroesophageal Adenocarcinoma Alisertib in Adults With Nonhematological Malignancies, Followed by Alisertib in Lung, Breast, Head and Neck or Gastroesophageal Malignancies PHASE1, PHASE2 COMPLETED
NCT01154816 Hepatoblastoma, Previously Treated Childhood Rhabdomyosarcoma, Recurrent Childhood Acute Lymphoblastic Leukemia, Recurrent Childhood Acute Myeloid Leukemia, Recurrent Childhood Kidney Neoplasm, Recurrent Childhood Malignant Germ Cell Tumor, Recurrent Childhood Rhabdomyosarcoma, Recurrent Childhood Soft Tissue Sarcoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Recurrent Neuroblastoma, Recurrent Osteosarcoma Alisertib in Treating Young Patients With Recurrent or Refractory Solid Tumors or Leukemia PHASE2 COMPLETED
NCT01639911 Malignant Neoplasm of Breast, CNS Malignancy, Malignant Neoplasm of Gastrointestinal Tract, Genitourinary Neoplasms Malignancy and Gender Unspecified, Head and Neck Neoplasms, Melanoma, Malignant Neoplasm of Thorax Phase I Study of MLN8237 and Pazopanib in Patients With Solid Tumors PHASE1 COMPLETED
NCT02530619 Acute Megakaryoblastic Leukemia, Myelofibrosis, Primary Myelofibrosis Alisertib in Treating Patients With Myelofibrosis or Relapsed or Refractory Acute Megakaryoblastic Leukemia NA UNKNOWN
NCT05718882 Liver Cancer, Hepatocellular Carcinoma, Resistant Cancer Lenvatinib Plus VIC-1911 in Lenvatinib-unresponsive or Lenvatinib-resistant HCC NA TERMINATED