ABI2

Gene Summary

Gene:ABI2; abl-interactor 2
Aliases: ABI-2, ABI2B, AIP-1, AblBP3, argBP1, SSH3BP2, argBPIA, argBPIB
Location:2q33
Summary:-
Databases:VEGA, OMIM, HGNC, Ensembl, GeneCard, Gene
Protein:abl interactor 2
Source:NCBIAccessed: 06 August, 2015

Ontology:

What does this gene/protein do?
Show (21)
Pathways:What pathways are this gene/protein implicaed in?
Show (2)

Cancer Overview

Research Indicators

Publications Per Year (1990-2015)
Graph generated 06 August 2015 using data from PubMed using criteria.

Literature Analysis

Mouse over the terms for more detail; many indicate links which you can click for dedicated pages about the topic.

  • Neoplasm Proteins
  • Mice, Transgenic
  • Infant
  • Cytoskeletal Proteins
  • Mutagenesis
  • Base Sequence
  • Abi1 protein, mouse
  • MLL
  • Chronic Myelogenous Leukemia
  • Amino Acid Sequence
  • Signal Transducing Adaptor Proteins
  • Abi2 protein, mouse
  • Proto-Oncogene Proteins c-abl
  • Bone Marrow
  • Proline
  • Fibronectins
  • Peptide Fragments
  • Ubiquitins
  • ABI2
  • Leukaemia
  • Acute Myeloid Leukaemia
  • ABI1
  • Multienzyme Complexes
  • src Homology Domains
  • Cell Line
  • Cysteine Endopeptidases
  • Chemotaxis
  • Homeodomain Proteins
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
  • Leukemic Gene Expression Regulation
  • Fusion Proteins, bcr-abl
  • Sequence Deletion
  • Translocation
  • Chromosome 2
  • Bone Marrow Transplantation
  • Protein Processing, Post-Translational
  • KMT2A
  • Transfection
  • Recombinant Proteins
  • ras Proteins
Tag cloud generated 06 August, 2015 using data from PubMed, MeSH and CancerIndex

Specific Cancers (3)

Data table showing topics related to specific cancers and associated disorders. Scope includes mutations and abnormal protein expression.

Note: list is not exhaustive. Number of papers are based on searches of PubMed (click on topic title for arbitrary criteria used).

Latest Publications: ABI2 (cancer-related)

Lechuga S, Baranwal S, Ivanov AI
Actin-interacting protein 1 controls assembly and permeability of intestinal epithelial apical junctions.
Am J Physiol Gastrointest Liver Physiol. 2015; 308(9):G745-56 [PubMed] Article available free on PMC after 01/05/2016 Related Publications
Adherens junctions (AJs) and tight junctions (TJs) are crucial regulators of the integrity and restitution of the intestinal epithelial barrier. The structure and function of epithelial junctions depend on their association with the cortical actin cytoskeleton that, in polarized epithelial cells, is represented by a prominent perijunctional actomyosin belt. The assembly and stability of the perijunctional cytoskeleton is controlled by constant turnover (disassembly and reassembly) of actin filaments. Actin-interacting protein (Aip) 1 is an emerging regulator of the actin cytoskeleton, playing a critical role in filament disassembly. In this study, we examined the roles of Aip1 in regulating the structure and remodeling of AJs and TJs in human intestinal epithelium. Aip1 was enriched at apical junctions in polarized human intestinal epithelial cells and normal mouse colonic mucosa. Knockdown of Aip1 by RNA interference increased the paracellular permeability of epithelial cell monolayers, decreased recruitment of AJ/TJ proteins to steady-state intercellular contacts, and attenuated junctional reassembly in a calcium-switch model. The observed defects of AJ/TJ structure and functions were accompanied by abnormal organization and dynamics of the perijunctional F-actin cytoskeleton. Moreover, loss of Aip1 impaired the apico-basal polarity of intestinal epithelial cell monolayers and inhibited formation of polarized epithelial cysts in 3-D Matrigel. Our findings demonstrate a previously unanticipated role of Aip1 in regulating the structure and remodeling of intestinal epithelial junctions and early steps of epithelial morphogenesis.

Kanaan Z, Qadan M, Eichenberger MR, Galandiuk S
The actin-cytoskeleton pathway and its potential role in inflammatory bowel disease-associated human colorectal cancer.
Genet Test Mol Biomarkers. 2010; 14(3):347-53 [PubMed] Article available free on PMC after 01/05/2016 Related Publications
INTRODUCTION: To improve our understanding of the various clinical phenotypes in inflammatory bowel disease (IBD)-associated colorectal cancer (CRC) and provide potential targets for early diagnosis and future therapy, we sought to identify new candidate genes and molecular pathways involved in the pathogenesis and progression of this disorder. Recent evidence has implicated the actin-cytoskeleton pathway in the development of metastatic sporadic CRC through cytoskeletal proteins such as fascin-1. We hereby propose that similar genetic polymorphisms and mutations among regulatory genes of the actin-cytoskeleton pathway may also be associated with increased dysplasia, carcinogenesis, and susceptibility for invasion and metastasis in IBD-associated CRC, as compared with sporadic CRC.
MATERIALS AND METHODS: To test this hypothesis, we identified three patients with IBD-associated CRC. We subsequently retrieved normal, dysplastic, and cancerous tissue from within the same surgical colonic specimen. Messenger RNA was subsequently isolated from fresh frozen tissue, and oligonucleotide arrays were carried out to identify genes that were differentially expressed between the three various tissue types (normal, dysplasia, and cancer). By utilizing the same specimen to obtain each of the three various tissue types, we excluded intersubject variability during the analysis. Finally, we performed bioinformatic interaction pathway analysis using the "Ingenuity Pathway Analysis" software.
RESULTS: Computerized pathway analysis revealed that the actin-cytoskeleton pathway was significantly dysregulated in the progression of normal cells, via dysplasia, to IBD-associated CRC (p < 0.05). Significantly up-regulated genes identified in the analysis included the fibroblast growth factor, Abelson interactor gene-2, profilin-2, and radixin genes. Conversely, the diaphanous homolog gene appeared to be significantly down-regulated.
CONCLUSION: Via the dysregulation of these five genes within the actin-cytoskeleton pathway, we propose that this molecular pathway provides a potential mechanism for the malignant transformation and progression of normal tissue, via dysplasia, to IBD-associated CRC.

Kano S, Miyajima N, Fukuda S, Hatakeyama S
Tripartite motif protein 32 facilitates cell growth and migration via degradation of Abl-interactor 2.
Cancer Res. 2008; 68(14):5572-80 [PubMed] Related Publications
Tripartite motif protein 32 (TRIM32) mRNA has been reported to be highly expressed in human head and neck squamous cell carcinoma, but the involvement of TRIM32 in carcinogenesis has not been fully elucidated. In this study, we found by using yeast two-hybrid screening that TRIM32 binds to Abl-interactor 2 (Abi2), which is known as a tumor suppressor and a cell migration inhibitor, and we showed that TRIM32 mediates the ubiquitination of Abi2. Overexpression of TRIM32 promoted degradation of Abi2, resulting in enhancement of cell growth, transforming activity, and cell motility, whereas a dominant-negative mutant of TRIM32 lacking the RING domain inhibited the degradation of Abi2. In addition, we found that TRIM32 suppresses apoptosis induced by cis-diamminedichloroplatinum (II) in HEp2 cell lines. These findings suggest that TRIM32 is a novel oncogene that promotes tumor growth, metastasis, and resistance to anticancer drugs.

Luo X, Levens E, Williams RS, Chegini N
The expression of Abl interactor 2 in leiomyoma and myometrium and regulation by GnRH analogue and transforming growth factor-beta.
Hum Reprod. 2006; 21(6):1380-6 [PubMed] Related Publications
BACKGROUND: Abelson (Abl) interactor 2 (Abi-2) has been considered as a key regulator of cell/tissue structural organization and is differentially expressed in leiomyomas. The objective of this study was to evaluate the expression of Abi-2 in leiomyoma/myometrium during the menstrual cycle and following GnRH analogue (GnRHa) therapy, as well as regulation by transforming growth factor (TGF)-beta1 in leiomyoma and myometrial smooth muscle cells (LSMC and MSMC).
METHODS: We used real-time PCR, Western blotting and immunohistochemistry to determine the expression of Abi-2 in paired leiomyoma and myometrium (n = 27) from proliferative (n = 8) and secretory (n = 12) phases of the menstrual cycle and from patients who received GnRHa therapy (n = 7). Time-dependent action of TGF-beta1 (2.5 ng/ml) and GnRHa (0.1 microM) on Abi-2 expression was determined in LSMC and MSMC.
RESULTS: Leiomyomas express elevated levels of Abi-2 as compared with myometrium from the proliferative but not the secretory phase of the menstrual cycle, with a significant reduction following GnRHa therapy (P < 0.05). Western blotting showed a similar trend in Abi-2 protein expression in leiomyoma/myometrial tissue extracts, which was immunolocalized in LSMC and MSMC, connective tissue fibroblasts and arterial walls. The expression of Abi-2 in LSMC and MSMC was increased by TGF-beta1 (2.5 ng/ml) and was inhibited by GnRHa (0.1 microM) in a time- and cell-dependent manner, and pretreatment with Smad3 SiRNA and U0126, an MEK-1/2 inhibitor, respectively, reversed their actions.
CONCLUSION: Based on the menstrual cycle-dependent expression, the influence of GnRHa therapy, and regulation by TGF-beta in LSMC/MSMC, we conclude that Abi-2 may have a key regulatory function in leiomyomas cellular/tissue structural organization during growth and regression.

Dai Z, Quackenbush RC, Courtney KD, et al.
Oncogenic Abl and Src tyrosine kinases elicit the ubiquitin-dependent degradation of target proteins through a Ras-independent pathway.
Genes Dev. 1998; 12(10):1415-24 [PubMed] Article available free on PMC after 01/05/2016 Related Publications
Oncogenic forms of the Abl and Src tyrosine kinases trigger the destruction of the Abi proteins, a family of Abl-interacting proteins that antagonize the oncogenic potential of Abl after overexpression in fibroblasts. The destruction of the Abi proteins requires tyrosine kinase activity and is dependent on the ubiquitin-proteasome pathway. We show that degradation of the Abi proteins occurs through a Ras-independent pathway. Significantly, expression of the Abi proteins is lost in cell lines and bone marrow cells isolated from patients with aggressive Bcr-Abl-positive leukemias. These findings suggest that loss of Abi proteins may be a component in the progression of Bcr-Abl-positive leukemias and identify a novel pathway linking activated nonreceptor protein tyrosine kinases to the destruction of specific target proteins through the ubiquitin-proteasome pathway.

Dai Z, Pendergast AM
Abi-2, a novel SH3-containing protein interacts with the c-Abl tyrosine kinase and modulates c-Abl transforming activity.
Genes Dev. 1995; 9(21):2569-82 [PubMed] Related Publications
A protein has been identified that interacts specifically with both the Src homologous 3 (SH3) domain and carboxy-terminal sequences of the c-Abl tyrosine kinase. The cDNA encoding the Abl interactor protein (Abi-2), was isolated from a human lymphocyte library using the yeast two-hybrid system with the Abl SH3 domain as bait. Abi-2 binds to c-Abl in vitro and in vivo. Abi-2 is a novel protein that contains an SH3 domain and proline-rich sequences critical for binding to c-Abl. A basic region in the amino terminus of Abi-2 is homologous to the DNA-binding sequence of homeo-domain proteins. We show that Abi-2 is a substrate for the c-Abl tyrosine kinase. Expression of an Abi-2 mutant protein that lacks sequences required for binding to the Abl SH3 domain but retains binding to the Abl carboxyl terminus activates the transforming capacity of c-Abl. The properties of Abi-2 are consistent with a dual role as regulator and potential effector of the c-Abl protein and suggest that Abi-2 may function as a tumor suppressor in mammalian cells.

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Cite this page: Cotterill SJ. ABI2, Cancer Genetics Web: http://www.cancer-genetics.org/ABI2.htm Accessed:

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