Biomarker: Aurora B

Histology type: endometrial carcinoma

Country: Japan

Region: Matsumoto

Followed up time :

Subgroup 1 name : positive

Subgroup 1 number: 25

Subgroup 2 name: negative

Subgroup 2 number: 48

Conclusion: Accordingly, the present study indicates the aberrant expression of Aurora A and Aurora B in endometrial carcinomas and the clinical importance of Aurora B expression in relationship to patient prognosis.

Sample type : tissue

Sample method: immunohistochemical/Western blotting/he reverse transcriptase polymerase chain reaction

Expression pattern : expression

Expression elevation: Immunoreactivity in the cytoplasm was evaluated by the percentage and the intensity (strong or weak) of positive cells among 500 cells in 5 high-power fields and calculated as follows: percentage of cells with intense staining _x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f
1 + percentage with weak staining
0.5. These results were described as a positivity index (PI), with a maximal score of 100. In endometrial carcinoma and hyperplasia, when there were no positive cells in the section (PI = 0), the case was defined as negative. When positive cells were present (PI N 0), the case was regarded as positive. When the PI was higher than 20, the case was defined as overexpression, according to a previous study

Funtion Uniprot: Serine/threonine-protein kinase component of the chromosomal passenger complex (CPC), a complex that acts as a key regulator of mitosis (PubMed:11516652, PubMed:12925766, PubMed:14610074, PubMed:14722118). The CPC complex has essential functions at the centromere in ensuring correct chromosome alignment and segregation and is required for chromatin-induced microtubule stabilization and spindle assembly (PubMed:11516652, PubMed:12925766, PubMed:14610074, PubMed:14722118, PubMed:26829474). Involved in the bipolar attachment of spindle microtubules to kinetochores and is a key regulator for the onset of cytokinesis during mitosis (PubMed:15249581). Required for central/midzone spindle assembly and cleavage furrow formation (PubMed:12458200, PubMed:12686604). Key component of the cytokinesis checkpoint, a process required to delay abscission to prevent both premature resolution of intercellular chromosome bridges and accumulation of DNA damage: phosphorylates CHMP4C, leading to retain abscission-competent VPS4 (VPS4A and/or VPS4B) at the midbody ring until abscission checkpoint signaling is terminated at late cytokinesis (PubMed:22422861, PubMed:24814515). AURKB phosphorylates the CPC complex subunits BIRC5/survivin, CDCA8/borealin and INCENP (PubMed:11516652, PubMed:12925766, PubMed:14610074). Phosphorylation of INCENP leads to increased AURKB activity (PubMed:11516652, PubMed:12925766, PubMed:14610074). Other known AURKB substrates involved in centromeric functions and mitosis are CENPA, DES/desmin, GPAF, KIF2C, NSUN2, RACGAP1, SEPTIN1, VIM/vimentin, HASPIN, and histone H3 (PubMed:11784863, PubMed:12689593, PubMed:14602875, PubMed:11856369, PubMed:16103226, PubMed:21658950, PubMed:11756469). A positive feedback loop involving HASPIN and AURKB contributes to localization of CPC to centromeres (PubMed:21658950). Phosphorylation of VIM controls vimentin filament segregation in cytokinetic process, whereas histone H3 is phosphorylated at 'Ser-10' and 'Ser-28' during mitosis (H3S10ph and H3S28ph, respectively) (PubMed:11784863, PubMed:11856369). A positive feedback between HASPIN and AURKB contributes to CPC localization (PubMed:21658950). AURKB is also required for kinetochore localization of BUB1 and SGO1 (PubMed:15020684, PubMed:17617734). Phosphorylation of p53/TP53 negatively regulates its transcriptional activity (PubMed:20959462). Key regulator of active promoters in resting B- and T-lymphocytes: acts by mediating phosphorylation of H3S28ph at active promoters in resting B-cells, inhibiting RNF2/RING1B-mediated ubiquitination of histone H2A and enhancing binding and activity of the USP16 deubiquitinase at transcribed genes (By similarity). Acts as an inhibitor of CGAS during mitosis: catalyzes phosphorylation of the N-terminus of CGAS during the G2-M transition, blocking CGAS liquid phase separation and activation, and thereby preventing CGAS-induced autoimmunity (PubMed:33542149). Phosphorylates KRT5 during anaphase and telophase (By similarity).

UniProt ID: Q96GD4

UniProt Link: https://www.uniprot.org/uniprotkb/Q96GD4/entry

Biological function from UniProt: #Cell cycle #Cell division #Mitosis

Molecular function from UniProt:

Tissue specificity from UniProt: High level expression seen in the thymus. It is also expressed in the spleen, lung, testis, colon, placenta and fetal liver. Expressed during S and G2/M phase and expression is up-regulated in cancer cells during M phase.Isoform 3 Not expressed in normal liver, high expression in metastatic liver.

Subcellular UniProt: #Centromere #Chromosome #Cytoplasm #Cytoskeleton #Kinetochore #Nucleus

Alternative name from UniProt:

Catalytic activity: ATP + L-seryl-[protein] = ADP + H+ + O-phospho-L-seryl-[protein];ATP + L-threonyl-[protein] = ADP + H+ + O-phospho-L-threonyl-[protein];

Recommended name: Aurora kinase B

Gene name from HGNC: AURKB (Aik2, AIM-1, ARK2, AurB, IPL1, PPP1R48, STK12, STK5)

HPA class: Cancer-related genes Disease related genes Enzymes Metabolic proteins Plasma proteins Potential drug targets

AlphaFold DB: Q96GD4

AlphaFold Link: https://alphafold.ebi.ac.uk/entry/Q96GD4

Induction: Expression is cell cycle-regulated, with a low in G1/S, an increase during G2 and M. Expression decreases again after M phase.

HPA link: https://www.proteinatlas.org/ENSG00000178999-AURKB

Tissue specificity RNA from HPA: Tissue enhanced (bone marrow, lymphoid tissue)

Tissue expression from HPA: Nuclear expression in several tissues, most abundant in immune cells of lymphoid tissues and gastrointestinal tract.

Single cell type specificity Cell type enhanced (Extravillous trophoblasts, Erythroid cells, Cytotrophoblasts, Hofbauer cells, Granulosa cells)

Immune cell specificity: Immune cell enhanced (T-reg)

Subcellular summary HPA Located in Nucleoplasm, Midbody (Single cell variability, CCD Protein, CCD Transcript)

Cancer prognostic summary HPA Prognostic marker in renal cancer (unfavorable) and liver cancer (unfavorable)

Pathology link: https://www.proteinatlas.org/ENSG00000178999-AURKB/pathology

Pathology endo: https://www.proteinatlas.org/ENSG00000178999-AURKB/pathology/endometrial+cancer

Disease: No disease ID

Note1: Disruptive regulation of expression is a possible mechanism of the perturbation of chromosomal integrity in cancer cells through its dominant-negative effect on cytokinesis

OMIM: 604970

OMIM link2: https://www.omim.org/entry/604970

HGNC ID: HGNC:11390

HGNC link: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:11390