DAB2IP

The following DAB2IP reagents supplied by CUSABIO are manufactured under a strict quality control system. Multiple applications have been validated and solid technical support is offered.

DAB2IP Antibodies

DAB2IP Antibodies for Homo sapiens (Human)

DAB2IP Proteins

DAB2IP Proteins for Mus musculus (Mouse)

DAB2IP Proteins for Homo sapiens (Human)

DAB2IP Proteins for Rattus norvegicus (Rat)

DAB2IP Background

Disabled homolog 2-interacting protein (DAB2IP) is a member of the RAS-GTPase-activating protein family, interacting with tumor suppressor DOC2/DAB2 and apoptosis signal-regulating kinase 1 (ASK1) [1][2]. DAB2IP was also called AIP1 (ASK (apoptosis signal-regulating kinase 1)-interacting protein 1). Structurally, DAB2IP contains several potential functional domains, including the Pleckstrin Homology (PH), Protein kinase C conserved region 2 (C2), GTPase-Activating Protein domain (GAP), Period-like domain (PER), Proline-rich domain (PR), and leucine zipper (LZ) domains. The PR domain in DAB2IP is critical for binding to the SH3 domain of the p85 regulatory subunit of PI3K. It is known that the C2 domain can interact with ASK1 to facilitate TNF-α-mediated apoptosis by activating ASK1. DAB2IP in metastatic prostate cancer (PCa) cells inhibits cell cycle progression by inducing G0 cell cycle arrest and promoting apoptosis under stress stimuli. It controls the balance between phosphatidylinositol 3-kinase (PI3K)-mediated cell survival and ASK1-mediated apoptosis [3][4]. The gain of function study showed that in the presence of PI3K inhibitor LY294002 (LY) or TNF-α, DAB2IP can inhibit the PI3K-Akt pathway and potentiate ASK1 activation, thus leading to cell apoptosis [5]. Whereas loss of DAB2IP resulted in PI3K-Akt activation and ASK1-JNK inactivation, which leads to accelerated PCa growth in vivo [5]. Since both agents can elicit the DAB2IP phosphorylation at Ser-604, suggesting that this site may be related to its conformation and critical for DAB2IP activity [5]. Therefore, DAB2IP is a scaffold protein that bridges both survival and death signal molecules.

[1] Wang Z, Tseng CP, et al. The mechanism of growth-inhibitory effect of DOC-2/DAB2 in prostate cancer. Characterization of a novel GTPase-activating protein associated with N-terminal domain of DOC-2/DAB2 [J]. J Biol Chem 2002; 277: 12622–12631.
[2] Zhang R, He X, et al. AIP1 mediates TNF-alpha-induced ASK1 activation by facilitating dissociation of ASK1 from its inhibitor 14-3-3 [J]. J Clin Invest 2003, 111: 1933–1943.
[3] Zhang H, Zhang R, et al. AIP1/DAB2IP, a novel member of the Ras-GAP family, transduces TRAF2-induced ASK1-JNK activation [J]. J Biol Chem 2004, 279: 44955–44965.
[4] Xie D, Gore C, et al. DAB2IP coordinates both PI3K-Akt and ASK1 pathways for cell survival and apoptosis [J]. Proc Natl Acad Sci U S A 2009, 106: 19878–19883.
[5] Daxing Xie, Crystal Gore, et al. DAB2IP coordinates both PI3K-Akt and ASK1 pathways for cell survival and apoptosis [J]. Proc Natl Acad Sci U S A. 2009 Nov 24; 106(47): 19878–19883.

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