benniegeorge authored almost 4 years ago

ABI interactor protein 1 (ABI1) is an adaptor protein. The human ABI1 gene is located on the 10p11.2 chromosome, and the encoded protein can form a complex with one or more protein molecules, regulating a variety of biological behaviors. The ABI1 protein contains 394 amino acid residues with a molecular weight of 42.5 kD. Gene sequence analysis showed that the ABI1 gene and its encoded protein sequence are highly similar, and 61% of the genes are expressed at the amino acid level. The amino acid terminal of ABI1 protein is rich in tryptophan/threonine (23%). The polyprotein proline structure in the middle of the protein plays a role in transcriptional activation of ABI1. The C3 end of the protein contains the SH3 domain (Src Homology 3 domain) mediates the interaction between proteins and proteins by linking to proline binding domains. Studies on the structure of ABI1 have shown that the SH3 domain or polyproline structure of ABI1 participates in the binding of ABI protein and plays a corresponding role. The detection results in human tissues show that ABI1 RNA is expressed in heart, brain, kidney, liver, lung, pancreas, skeletal muscle, peripheral blood cells, placenta and other tissues in adults.

Some studies have shown that ABI1 inhibits cell proliferation. In the highly invasive human breast cancer cell line MDA-MB-231, the expression of ABI1 was increased, knocking down its expression and inhibiting the cell proliferation and cell clonality of the cell line, indicating that ABI1 can promote the proliferation of breast cancer cells. In human colon cancer tissues, the NADPH oxidase binding protein p47 (phox) is inhibited, and overexpression of p47 (phox) enhances the apoptosis of colon cancer cell lines. Co-immunoprecipitation assays revealed that p47(phox) was co-precipitated with ABI1 and c-ABl in colon cancer cells. The ectopic expression of p47 (phox) in colon cancer cells phosphorylates c-ABI1, increases oxidation products, and promotes apoptosis.

Membrane-type 1 matrix metalloproteinase (MT1-MMP) is a member of the transmembrane metalloproteinase family and plays an important role in the degradation of cell matrices, thereby regulating cell migration and invasion. In Bcr-ABl-positive leukemia cells, the distribution of MT1-MMP is consistent with the distribution of F-actin-rich structures, and the ABI1 pathway is essential in maintaining the polar distribution of MT1-MMP. The knock-down of ABI1 in p185wt-Bcr-Abl-positive leukemia cells with small hairpin RNA (shRNA) technology can significantly inhibit Bcr-ABl-induced intracellular MT1-MMP polarity distribution, inhibiting cell invasion and migration.

ABI1 is closely related to the occurrence and development of some types of leukemia and some malignant solid tumors. Therefore, ABI1 shows a broad research prospect as a potential molecular target in the basic and clinical research of tumors. ABI1 is a binding partner of c-Abl, oncogenic v-Abl, and Bcr-Abl tyrosine kinases. More than 95% of patients with chronic myeloid leukemia and some acute lymphoblastic leukemia have Bcr-Abl expression. Tyrosine phosphorylation occurs in ABI1 in Bcr-Abl-positive leukemia cells.

Chorzalska et al. proposed that signal crosstalk between α4 integrin and Abelson interacting protein-1 (ABI-1) involves the acquisition of anchorage-dependent phenotypes and drug resistance in Bcr-Abl positive leukemia cells. Comparison of ABI1 and α4 integrin (ITGA4) gene expression in relapsed Bcr-Abl-positive CD34 + progenitors revealed a decrease in ABI1 and an increase in α4 integrin mRNA mutations in the absence of Bcr-ABl. This anti-correlation between ABI1 and α4 integrin expression and attachment to elevated phospho-Akt and phospho-Erk signaling was confirmed in imatinib mesylate resistant leukemic cells. These results indicate that the α4-ABI1 signaling pathway can mediate the acquisition of a resistant phenotype of leukemia cells. The study also found that in Bcr-ABl-positive leukemia cells, ABI1 is characterized by co-localization with abnormally aggregated F-actin, which enhances leukemic cell adhesion and locomotor activity. These results suggest that ABI1 plays a key role in the adhesion, migration, and invasion of leukemia cells.

ABI1, as a conjugate protein, also regulates cell motility by forming macromolecular complexes involved in actin remodeling and lamellipodia formation. The Abelson tyrosine kinase (c-ABl) inhibitor STI571 has been shown to effectively inhibit the migration and invasion of colorectal cancer cells. ABI1 is a key regulator of actin reorganization and is up-regulated in colorectal cancer. Steinestel et al. investigated the role of ABI1 in extracellular matrix degradation and targeted ABI1 phosphorylation in colorectal cancer invasiveness, demonstrating that phosphorylated ABI1 contributes to the aggressiveness of colorectal cancer. This group also discovered the central role of phosphorylated ABI1 in the formation of lamellipodia-like protuberances, a prerequisite for cell migration of colorectal cancer cells. Since the phosphorylation of ABI1 can be pharmacologically targeted with STI571, suggesting that a possible therapeutic option is to prevent the increase of the metastatic phenotype in colorectal cancer.

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