Disease relevance of HBXIP

• We show that survivin forms complexes with a cellular protein, hepatitis B X-interacting protein (HBXIP), which was originally recognized for its association with the X protein of hepatitis B virus (HBX) [1].
• In contrast, the replication levels of the duck hepatitis B virus, a hepadnavirus that lacks the x open reading frame, were unchanged in the context of XIP expression [2].
• Investigation of the role of XIP in hepatitis B virus replication in differentiated hepatocellular carcinoma cells revealed that XIP expression reduces wild-type hepatitis B virus replication to levels observed following transfection with an HBx-minus virus [2].

High impact information on HBXIP

• We further show that acyl CoAs may interact directly with the XIP (exchanger inhibitory peptide) sequence, a known region of anionic lipid modulation, to dynamically regulate NCX1 activity and Ca(2+) homeostasis [3].
• HBXIP functions as a cofactor of survivin in apoptosis suppression [1].
• As defined by the HUMARA assay, 53 of 78 patients had persistent polyclonal hematopoiesis, 15 of 78 had skewed XIP, and 10 of 78 (13.5%) either had clonal hematopoiesis at the time of ABMT or developed clonal hematopoiesis after ABMT. t-MDS/AML developed in 2 of 53 patients with polyclonal hematopoiesis and in 4 of 10 with clonal hematopoiesis [4].
• At the time of ABMT, the prevalence of polyclonal hematopoiesis was 77% (80/104), of skewed X-inactivation pattern (XIP) was 20% (21/104), and of clonal hematopoiesis was 3% (3/104) [4].
• Thus, viral HBx and its cellular target HBXIP regulate centrosome dynamics and cytokinesis affecting genetic stability [5].

Chemical compound and disease context of HBXIP

• HBXIP, Cellular Target of Hepatitis B Virus Oncoprotein, Is a Regulator of Centrosome Dynamics and Cytokinesis [5].

Biological context of HBXIP

• We propose that one of the physiologic functions of the cellular protein XIP is to negatively regulate HBx activity and thus to alter the replication life cycle of the virus [2].
• Thus, HBXIP is a critical regulator of hepatocyte cell growth in vivo, making it a strong candidate for explaining the tumorigenic actions of viral HBx [5].
• The hepatitis B virus genome encodes an oncoprotein, HBx, which binds various cellular proteins including HBXIP [5].
• We found that most cells deficient in HBXIP arrest in prometaphase with monopolar spindles whereas HBXIP overexpression causes tripolar or multipolar spindles due to excessive centrosome replication [5].
• In vivo experiments using antisense oligonucleotides targeting HBXIP in a mouse model of liver regeneration showed a requirement for HBXIP for growth and survival of replicating hepatocytes [5].

Anatomical context of HBXIP

• Additionally, a defect in cytokinesis was seen in HBXIP-deficient HeLa cells, with most cells failing to complete division and succumbing eventually to apoptosis [5].
• Immunolocalization and fluorescent protein tagging experiments showed that HBXIP associates with microtubules of dividing cells and colocalizes with HBx on centrosomes [5].
• We show here that HBXIP is a regulator of centrosome duplication, required for bipolar spindle formation in HeLa human carcinoma cells and primary mouse embryonic fibroblast cells [5].
• The inhibitory effects of Na+/Ca2+ exchange inhibitory peptide (XIP), which corresponds to residues 219-238 of the Na+/Ca2+ exchange protein from canine heart, were studied in both rat and human brain plasma membrane vesicles [6].
• By whole-cell voltage clamping experiments, we demonstrate that deletion of residues 562-679, but not 440- 456, 498-510, or 680-685 of the f-loop selectively eliminates XIP-mediated inhibition of NCX expressed either heterologously (HEK293 and A549 cells) or in guinea pig cardiac myocytes [7].

Associations of HBXIP with chemical compounds

• Furthermore, the role of the relatively recently discovered cereal endoxylanase inhibitor families TAXI (Triticum aestivum xylanase inhibitor) and XIP (xylanase inhibitor protein) in plant defense is discussed [8].
• Also, contractions that are activated in the presence of nifedipine are sensitive to the Na-Ca exchange inhibitor XIP [9].
• Use of cysteine replacements and chemical modification to alter XIP, the autoinhibitory region of the Na-Ca exchanger. Inhibition of the activated plasma membrane Ca pump [10].
• Sulfosuccinimidyl acetate (SNA)-modified XIP does not inhibit the Ca pump; SNA neutralizes the positive charge on Lys at positions 7, 11, and 17 [11].
• Three peptide analogues, in which 7, 11, and 17 were Ala, Cys, or Lys, inhibited about as well as XIP [11].

Other interactions of HBXIP

• CONCLUSION: Elevated levels of GDN/PN1 and XIP mRNAs induced by Allitridi provide valuable molecular evidence for elucidating the garlic's efficacies against neurodegenerative and inflammatory diseases [12].
• In the cytoplasm, survivin inhibits apoptosis by interacting with caspase-9 in the presence of the HBXIP cofactor, by binding to Smac or associating with XIAP [13].
• From yeast two hybrid screening with HBX as bait, human guanine nucleotide binding protein beta subunit 5L (GNbeta5) was isolated from the cDNA library constructed in this study as a new HBX-interacting protein [14].

Analytical, diagnostic and therapeutic context of HBXIP

• The above mentioned A. aculeatus endoxylanase was not inhibited either, although gel permeation chromatography revealed that it complexed rice XIP in a 1:1 molar stoichiometric ratio [15].
• A rice XIP-type inhibitor was purified by affinity chromatography with an immobilized Aspergillus aculeatus family 10 endoxylanase [15].

References