Disease relevance of DAB2IP

• Down-regulation of human DAB2IP gene expression mediated by polycomb Ezh2 complex and histone deacetylase in prostate cancer [1].
• We analyzed methylation and expression status of hDAB2IP in breast cancer [2].
• Our results demonstrate that hDAB2IP methylation frequently is present in breast cancer and plays a key role in hDAB2IP inactivation, suggesting the relationship between hDAB2IP methylation and lymph node metastasis of breast cancer [2].
• We analyzed the methylation and expression status of hDAB2IP in lung cancers [3].
• The promoter region of hDAB2IP was divided into two regions (m2a and m2b) based on our previous report, and the methylation status was determined by bisulphite DNA sequencing in gastric cancer cell lines [4].

High impact information on DAB2IP

• In contrast to 14-3-3, AIP1 binds preferentially to dephosphorylated ASK1 [5].
• The T123A mutant p53 displayed significantly better DNA binding in vitro as well as stronger transactivation and apoptotic activity in vivo than wild-type p53, particularly toward its pro-apoptotic target AIP1 [6].
• We further unveiled that the methylation status of Lys-27 but not Lys-9 of H3 in hDAB2IP promoter region is consistent with the hDAB2IP levels in both normal prostatic epithelial cells and PCa cells [1].
• In this study, we have demonstrated that an increased Ezh2 expression in normal prostatic epithelial cells can suppress hDAB2IP gene expression [1].
• Human DAB2IP (hDAB2IP), a novel GTPase-activating protein modulating the Ras-mediated signaling and tumor necrosis factor-mediated apoptosis, is a potent growth inhibitor in human prostate cancer (PCa) [1].

Chemical compound and disease context of DAB2IP

• The methylation status of hDAB2IP was examined in lung cancer cell lines using bisulfite sequencing and MSP [3].

Biological context of DAB2IP

• These data indicate that transcriptional regulation of DAB2IP is responsible for the downregulation of DAB2IP expression in prostate cancer cells [7].
• Loss of hDAB2IP expression in PCa is due to altered epigenetic regulation (i.e. DNA methylation and histone modification) of its promoter region [1].
• Epigenetic regulation of a novel tumor suppressor gene (hDAB2IP) in prostate cancer cell lines [8].
• Analysis of the hDAB2IP promoter revealed that it is a typical TATA-less promoter containing many GC-rich sequences [8].
• Acetylhistone H3 was associated with the hDAB2IP promoter, and CpG islands remained almost unmethylated in normal prostatic epithelia, but not in PCa cell lines [8].

Anatomical context of DAB2IP

• We demonstrated that DAB2IP is often downregulated in human prostate cancer cell lines [7].
• We further demonstrated that normal prostatic epithelial cells have elevated DAB2IP mRNA compared with cancer cells, which correlates with increased DAB2IP promoter activity [7].
• Together, we conclude that hDAB2IP gene is a target gene of Ezh2 in prostatic epithelium, which provides an underlying mechanism of the down-regulation of hDAB2IP gene in PCa [1].

Associations of DAB2IP with chemical compounds

• AIP1 binds to the C-terminal domain of ASK1 via a lysine-rich cluster within the N-terminal C2 domain [5].
• Our data further indicated that trichostatin A (histone deacetylase inhibitor) and 5'-aza-2'-deoxycytidine (DNA hypomethylation agent) acted cooperatively in modulating hDAB2IP gene expression in PCa, whereas histone acetylation played a more significant role in this event [8].

Other interactions of DAB2IP

• Previously we have shown that ASK-interacting protein 1 (AIP1, also known as DAB2IP), a novel member of the Ras-GAP protein family, mediates TNF-induced activation of ASK1-JNK signaling pathway [9].
• Human DAB2IP (for DAB2 interaction protein) is a novel member of the RasGTPase-activating protein family [7].
• In conclusion, aberrant methylation and abnormal protein expression of the caveolin-1-gene is involved in the formation of nonurothelial carcinomas of the urinary bladder and promoter methylation of the hDAB2IP gene in the progression of TCC from a low to a high malignant potential [10].
• From an AML-M5 with a t(9;11)(q34;q23), we identified a novel MLL fusion partner, AF9Q34 [11].

Analytical, diagnostic and therapeutic context of DAB2IP

• CONCLUSIONS: We developed methylation-specific PCR for hDAB2IP and examined its methylation status in breast cancer [2].
• Expression was examined using conventional and real-time RT-PCR, and methylation was found to be inversely correlated with expression, confirming that the MSP can also be used to examine hDAB2IP methylation status in lung cancers [3].

References