Disease relevance of ITGB3BP

• In addition, NRIF3 deregulation enhanced the responsiveness of breast cancer cells to estrogen-induced stimulation of growth and anchorage independence [1].
• Here, we show that the long form of beta3-endonexin (EN-L) can be detected in platelet lysates several hours after thrombus formation, after long-term storage of platelets and after glucose deprivation [2].

High impact information on ITGB3BP

• The cytoplasmic domains of integrins are required for the transduction of this bidirectional information, and have recently been shown to participate in direct interactions with some novel cytoplasmic proteins, such as an ankyrin repeat containing serine/threonine protein kinase (integrin-linked kinase) and beta3 endonexin [3].
• Thus, the discovery of TAP20, which interacts with integrin beta5 and modulates cell adhesion, migration, and tube formation, further defines a possible pathway to angiogenesis dependent on PKCtheta [4].
• Enhancement of endothelial cell migration and in vitro tube formation by TAP20, a novel beta 5 integrin-modulating, PKC theta-dependent protein [4].
• Overexpression of TAP20 also decreased focal adhesion formation in alphavbeta3-deficient cells [4].
• Affinity modulation of alphaIIbbeta3 by GFP/beta3-endonexin was inhibited by coexpression of either a monomeric beta3 cytoplasmic tail chimera or an activated form of H-Ras [5].

Biological context of ITGB3BP

• By using Gal4 fusion constructs, we identified an autonomous transactivation domain (AD1) at the C terminus of NRIF3 [6].
• The NRIF3 family of transcriptional coregulators induces rapid and profound apoptosis in breast cancer cells [7].
• Domain and mutagenesis analyses indicated that a novel C-terminal domain in NRIF3 plays an essential role in its specific interaction with liganded TR and RXR while the N-terminal LXXLL motif plays a minor role in allowing optimum interaction [8].
• The NRIF3 gene encodes at least two additional isoforms due to alternative splicing [6].
• Interestingly, a single amino acid residue change of a potential phosphorylation site in RepD1 (Ser(28) to Ala) abolishes its transrepression function, suggesting that the coregulatory property of NRIF3 (or its isoforms) might be subjected to regulation by cellular signaling [6].

Anatomical context of ITGB3BP

• When beta3-endonexin was fused to green fluorescent protein (GFP) and transfected into CHO cells, it was found in both the cytoplasm and the nucleus and could be detected on Western blots of cell lysates [5].
• Fluorescence microscopy shows that NRIF3 localizes to the cell nucleus [8].
• We report here that expression of the NRIF3 family of transcriptional coregulators in a variety of breast cancer cell lines induces rapid and profound apoptosis (nearly 100% cell death within 24 h) [7].

Associations of ITGB3BP with chemical compounds

• Beta 3-endonexin, a novel polypeptide that interacts specifically with the cytoplasmic tail of the integrin beta 3 subunit [9].

Physical interactions of ITGB3BP

• NRIF3 interacted with MTA1 both in vitro and in vivo [1].
• This process may be triggered by a regulatory molecule(s) that binds to the integrin cytoplasmic tails, causing a structural change in the receptor. beta3-Endonexin is a novel 111-amino acid protein that binds selectively to the beta3 tail [5].

Regulatory relationships of ITGB3BP

• MTA1 repressed NRIF3-mediated stimulation of ERE-driven transcription and interfered with NRIF3's association with the ER target gene chromatin [1].

Other interactions of ITGB3BP

• With a yeast two-hybrid screen to clone MTA1-interacting proteins, we identified a known nuclear receptor coregulator (NRIF3) as an MTA1-binding protein [1].
• Here we report the cloning and analysis of a novel nuclear receptor coactivator (designated NRIF3) that exhibits a distinct receptor specificity [8].
• beta3-endonexin as a novel inhibitor of cyclin A-associated kinase [10].
• The apparent specificity of beta 3-endonexin for the beta 3 integrin subunit suggests potential mechanisms for selective modulation of integrin functions [9].
• Deletion and mutagenesis analyses mapped the dimerization domain to a region in the middle of NRIF3 (residues 84 to 112), which is predicted to form a coiled-coil structure and contains a putative leucine zipper-like motif [6].

Analytical, diagnostic and therapeutic context of ITGB3BP

• The interaction between TAP20 and beta5 integrin cytoplasmic domain was demonstrated by protein coprecipitation and immunoblotting [4].

References