Functional characterization of AIBp, a novel Aurora-A binding protein in centrosome structure and spindle formation

Lieu, Ann-Shung; Cheng, Tai Shan; Chou, Chia Hua; Wu, Chia‐Hung; Hsu, Chia‐Yi; Huang, Chi Ying F.; Chang, Li; Loh, Joon Khim; Chang, Chung Shing; Hsu, Che-Wei; Howng, Shen Long; Hong, Yi‐Ren

doi:10.3892/ijo_00000691

Cited by 7 publications

(5 citation statements)

References 17 publications

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“…Ninein is phosphorylated by GSK3␤, Aurora A, and PKA (36,38,39). This phosphorylation is tightly regulated: centrosomal protein CGI-99 blocks ninein phosphorylation by GSK3␤ (36), and Aurora Abinding protein (AIBp) prevents the phosphorylation of ninein by both Aurora A and GSK3␤ (81). Ninein has been identified in a screen for proteins that were tyrosyl phosphorylated in response to vascular endothelial growth factor (VEGF) during tubular morphogenesis of endothelial cells (82).…”

Section: Discussionmentioning

confidence: 99%

JAK2 Tyrosine Kinase Phosphorylates and Is Negatively Regulated by Centrosomal Protein Ninein

Jay

Hammer

Nestor-Kalinoski

et al. 2015

Molecular and Cellular Biology

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JAK2 is a cytoplasmic tyrosine kinase critical for cytokine signaling. In this study, we have identified a novel centrosome-associated complex containing ninein and JAK2. We have found that active JAK2 localizes around the mother centrioles, where it partly colocalizes with ninein, a protein involved in microtubule (MT) nucleation and anchoring. We demonstrated that JAK2 is an important regulator of centrosome function. Depletion of JAK2 or use of JAK2-null cells causes defects in MT anchoring and increased numbers of cells with mitotic defects; however, MT nucleation is unaffected. We showed that JAK2 directly phosphorylates the N terminus of ninein while the C terminus of ninein inhibits JAK2 kinase activity in vitro. Overexpressed wild-type (WT) or C-terminal (amino acids 1179 to 1931) ninein inhibits JAK2. This ninein-dependent inhibition of JAK2 significantly decreases prolactin-and interferon gamma (IFN-␥)-induced tyrosyl phosphorylation of STAT1 and STAT5. Downregulation of ninein enhances JAK2 activation. These results indicate that JAK2 is a novel member of centrosome-associated complex and that this localization regulates both centrosomal function and JAK2 kinase activity, thus controlling cytokine-activated molecular pathways. JAK2 is a tyrosine kinase that is activated by two-thirds of the cytokine/hematopoietin receptor superfamily. JAK2 activation initiates a variety of downstream signaling events that lead to diverse physiological responses to cytokines, including regulation of body growth, hematopoiesis, satiety, lactation, and various immune functions. Upon activation, receptor-bound JAK2 phosphorylates specific tyrosine residues of its downstream targets, activating cell survival/proliferation-promoting signaling pathways (1). One target of JAK2 is a family of transcription factors termed signal transducers and activators of transcription (STATs). STATs exist within the cytoplasm in a latent or inactive state; they are recruited by cytokine receptor complexes through interaction between the receptor or JAK phosphotyrosines and the Src homology 2 (SH2) domain of the STAT protein. Several additional kinase cascades may be activated by JAK2, including phosphoinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways. Three mechanisms of JAK2 activation at the genetic level have been implicated in hematologic malignancies: point mutations, translocations, and amplifications (reviewed in reference 2). Mutations within the pseudokinase domain of JAK2 were detected in a spectrum of myeloproliferative diseases. A V617F gain-of-function point mutation is the cause of ϳ90% of all polycythemia vera cases and ϳ50% of all essential thrombocythemia and primitive myelofibrosis cases (3, 4). Several additional mutations leading to constitutively active JAK2 have been identified recently in patients, including a JAK2 K539L mutant. A T875N substitution in JAK2 was also identified in megakaryoblastic myeloid leukemia cells. In a patient with trisomy 21 and B cell precursor acute lymphoblastic l...

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Section: Discussionmentioning

confidence: 99%

JAK2 Tyrosine Kinase Phosphorylates and Is Negatively Regulated by Centrosomal Protein Ninein

Jay

Hammer

Nestor-Kalinoski

et al. 2015

Molecular and Cellular Biology

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“…It has become a priority therapeutic target for treating cancer (34). AUNIP interacts with the C-terminus of Aurora-A, which is necessary for Aurora-A to move dynamically at centrosomes and the spindle apparatus during the cell cycle (11). Based on our enrichment analysis, AUNIP was associated with the cell cycle ( Figures 6C, H).…”

Section: Discussionmentioning

confidence: 83%

“…AUNIP (Aurora kinase A and ninein-interacting protein) is responsible for maintaining the centrosomal structure and facilitating spindle formation (11). AUNIP has not been thoroughly researched, but it is a potential prognostic biomarker for OSCC.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, identifying further prognostic biomarkers and possible therapeutic targets is of great significance. AUNIP (Aurora kinase A [Aurora-A] and ninein-interacting protein), also known as AIBp and C1orf135, is a centrosome protein that promotes the maintenance of the centrosome structure and the formation of the spindle by interacting with Aurora-A and Ninein (11). AUNIP can control Plk1 and Aurora-A activation, thereby modulating mitotic entry and mitotic spindle assembly (12).…”

Section: Introductionmentioning

confidence: 99%

“…AUNIP can control Plk1 and Aurora-A activation, thereby modulating mitotic entry and mitotic spindle assembly (12). Moreover, high AUNIP expression has been detected in brain tumors (11). Furthermore, recent research has found that AUNIP regulates the cell cycle of oral squamous cell carcinoma (OSCC) cells and can be used as a prognostic biomarker for OSCC.…”

Section: Introductionmentioning

confidence: 99%

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AUNIP Expression Is Correlated With Immune Infiltration and Is a Candidate Diagnostic and Prognostic Biomarker for Hepatocellular Carcinoma and Lung Adenocarcinoma

Kang

et al. 2020

Front. Oncol.

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AUNIP, a novel prognostic biomarker, has been shown to be associated with stromal and immune scores in oral squamous cell carcinoma (OSCC). Nonetheless, its role in other cancer types was unclear. In this study, AUNIP expression was increased in hepatocellular carcinoma (HCC) and lung adenocarcinoma (LUAD) according to data from The Cancer Genome Atlas (TCGA) database, Integrative Molecular Database of Hepatocellular Carcinoma (HCCDB), and Gene Expression Omnibus (GEO) database (GSE45436, GSE102079, GSE10072, GSE31210, and GSE43458). Further, according to copy number variation analysis, AUNIP up-regulation may be associated with copy number variation. Immunohistochemistry showed AUNIP expression was higher in HCC and LUAD compared with the normal tissues. Receiver operating characteristic (ROC) curve analysis demonstrated that AUNIP is a candidate diagnostic biomarker for HCC and LUAD. Next, TCGA, International Cancer Genome Consortium (ICGC), and GEO (GSE31210 and GSE50081) data showed that increased AUNIP expression clearly predicted poor overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) in HCC and LUAD. Additionally, multivariate Cox regression analysis involving various clinical factors showed that AUNIP is an independent prognostic biomarker for HCC and LUAD. Next, the role of AUNIP in HCC and LUAD was explored via a co-expression analysis, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, and a gene set variation analysis (GSVA). HCC and LUAD exhibited almost identical enrichment results. More specifically, high AUNIP expression was associated with DNA replication, cell cycle, oocyte meiosis, homologous recombination, mismatch repair, the p53 signal transduction pathway, and progesterone-mediated oocyte maturation. Lastly, the Tumor Immune Estimation Resource (TIMER) tool was used to determine the correlations of AUNIP expression with tumor immune infiltration. AUNIP expression was positively correlated with the infiltration degree of B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and dendritic cells in HCC. However, AUNIP expression was negatively correlated with the infiltration degree of B cells, CD4+ T cells, and macrophages in LUAD. In addition, AUNIP expression was correlated with immune infiltration in various other tumors. In conclusion, AUNIP, which is associated with tumor immune infiltration, is a candidate diagnostic and prognostic biomarker for HCC and LUAD.

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Identification of AUNIP as a candidate diagnostic and prognostic biomarker for oral squamous cell carcinoma

Yang

Liang

et al. 2019

EBioMedicine

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BackgroundOral squamous cell carcinoma (OSCC) is one of the most common malignant tumors worldwide. Patients with poorly differentiated OSCC often exhibit a poor prognosis. AUNIP (Aurora Kinase A and Ninein Interacting Protein), also known as AIBp, plays a key role in cell cycle and DNA damage repair. However, the function of AUNIP in OSCC remains elusive.MethodsThe differentially expressed genes (DEGs) were obtained using R language. Receiver operating characteristic curve analysis was performed to identify diagnostic markers for OSCC. The effectiveness of AUNIP in diagnosing OSCC was evaluated by machine learning. AUNIP expression was analyzed in publicly available databases and clinical specimens. Bioinformatics analysis and in vitro experiments were conducted to explore biological functions and prognostic value of AUNIP in OSCC.FindingsThe gene integration analysis revealed 90 upregulated DEGs. One candidate biomarker, AUNIP, for the diagnosis of OSCC was detected, and its expression gradually increased along with malignant differentiation of OSCC. Bioinformatics analysis demonstrated that AUNIP could be associated with tumor microenvironment, human papillomavirus infection, and cell cycle in OSCC. The suppression of AUNIP inhibited OSCC cell proliferation and resulted in G0/G1 phase arrest in OSCC cells. The survival analysis showed that AUNIP overexpression predicted poor prognosis of OSCC patients.Interpretation: AUNIP could serve as a candidate diagnostic and prognostic biomarker for OSCC and suppression of AUNIP may be a potential approach to preventing and treating OSCC.FundTaishan Scholars Project in Shandong Province (ts201511106) and the National Natural Science Foundation of China (Nos. 61603218).

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Functional characterization of AIBp, a novel Aurora-A binding protein in centrosome structure and spindle formation

Cited by 7 publications

References 17 publications

JAK2 Tyrosine Kinase Phosphorylates and Is Negatively Regulated by Centrosomal Protein Ninein

JAK2 Tyrosine Kinase Phosphorylates and Is Negatively Regulated by Centrosomal Protein Ninein

AUNIP Expression Is Correlated With Immune Infiltration and Is a Candidate Diagnostic and Prognostic Biomarker for Hepatocellular Carcinoma and Lung Adenocarcinoma

Identification of AUNIP as a candidate diagnostic and prognostic biomarker for oral squamous cell carcinoma

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