Disease relevance of Akp3

• However, when maintained long-term on a high-fat diet, the IAP-deficient mice showed faster body weight gain than did control animals [1].
• We used the retroviral vector for transducing IAP gene into SNU638 gastric cancer cells and EP was prepared by phosphorylation of etoposide [2].
• Both a point mutation in the baculovirus IAP repeat motif (C84A) and a COOH-terminal deletion mutant (Delta106) of survivin fail to localize to either kinetochores or midbodies, but neither interferes with cell cleavage [3].
• The HERV-K LTR, however, had little sequence homology to either the IAP LTR or other typical oncovirus LTRs [4].
• The cloned mouse mammary tumor virus (type B) gene was found to hybridize with both the HERV-K and IAP genes to essentially the same extent [4].

High impact information on Akp3

• We have marked a cloned mouse IAP sequence with a neomycin-containing indicator gene whose expression is conditioned by passage of the transposon through an RNA intermediate [5].
• Using cloned fragments of IAP genes as labeled probes in dot-hybridization experiments, we detected IAP-related RNA sequences in mouse oocytes and preimplantation embryos [6].
• Histological examination revealed an accelerated transport of fat droplets through the intestinal epithelium and elevation of serum triglyceride levels in the IAP-deficient mice compared to wild-type mice [1].
• We inactivated the mouse IAP gene in embryo-derived stem cells and generated mice homozygous for the null mutation [1].
• Therefore, expression of IAP in the nontumorigenic HeLa x fibroblast cell hybrid is not sufficient to confer the tumorigenic phenotype [7].

Chemical compound and disease context of Akp3

• Islet-activating protein or pertussis toxin pretreatment hardly influenced the increase in intracellular Ca2+ and inositol trisphosphate production induced by ATP, suggesting that IAP-sensitive GTP-binding proteins do not play a practical role in this reaction [8].

Biological context of Akp3

• This observation suggests that a putative HeLa tumor suppressor gene(s) is located on chromosome 11 and that this gene may be a negative regulator of the IAP gene [9].
• An exclusive correlation exists between the ectopic expression of the cell-surface marker, intestinal alkaline phosphatase (IAP), and the tumorigenic phenotype of segregants derived from suppressed, nontumorigenic HeLa x fibroblast cell hybrids [7].
• However, studies with tumor reconstitutes of the GIMs and transfection studies with an IAP complementary DNA expression vector indicate that high IAP expression alone is not sufficient to confer rapid tumor growth [9].
• Sequence analysis of the HeLa IAP cDNA revealed 5 separate nucleotide alterations when compared to the native IAP cDNA sequence; however, none of these resulted in amino acid substitutions [7].
• We have now begun to investigate the molecular basis of radiation-induced neoplastic transformation in this system by studying the potential genetic linkage between p75/IAP expression, tumorigenicity and damage to a putative tumor suppressor locus on fibroblast chromosome 11 [10].

Anatomical context of Akp3

• Previous analysis of spontaneous segregants of the nontumorigenic hybrid have implicated the loss of one copy of human fibroblast chromosome 11 with reexpression of IAP and tumorigenicity [9].
• Fusion of tumorigenic HeLa cells with human skin fibroblasts results in genetically stable hybrids which are nontumorigenic and no longer express the HeLa tumor-associated antigen, intestinal alkaline phosphatase (IAP) [9].
• Control cell lines which were negative for p75-IAP (CONs) were also isolated from irradiated populations, and none were found to be tumorigenic [10].
• Furthermore, T cell proliferation was observed when a highly purified IAP fragment (CNBr 21) spanning amino acids 334-462 of the primary structure of IAP was used as antigen [11].
• Double immunocytochemical staining of T cell-depleted PBMC with IAP and an anti-human CD5 antibody allowed the detection of CD5+ B lymphocytes, which probably produce natural IAPA (nIAPA) [11].

Associations of Akp3 with chemical compounds

• Programmed cell death in the mammary gland is associated with the expression of the growth arrest gene, gas-1, and the integrin-associated protein gene, IAP, which codes for a putative Ca2+ channel that is dependent on integrin [12].
• These findings suggested that one of the pathways of adipocyte differentiation induced by hormones/IBMX occurs via the inositolglycan-specific PI-PLC cascade coupled to IAP-sensitive G-protein(s) [13].
• Strain LOU/Iap, which is known to have been genetically contaminated in the past, was clearly different from strain LOU/CN, supporting previous findings of studies using biochemical markers [14].

Other interactions of Akp3

• The minimum size of the Spr deletion would therefore be limited to 14 cM, the genetic distance between Vil and Akp-3 [15].
• The closest distal marker to the deletion is the Acrg gene, with the distal deletion breakpoint mapping within the 0.8-cM segment separating Akp-3 and Acrg [15].
• The available data do not reveal the genetic basis for the faster migration rate of the enzyme from the SWR/J strain, but a different response to neuraminidase and apparent nonlinkage to the Pep-3 locus suggest that a locus other than Akp-3 is responsible [16].
• In particular, the differences seen in the Bcl-2 and IAP families are consistent with the antiapoptotic responses observed in the resistant wild-type cells compared with the sensitive p65-/- fibroblasts [17].
• Previous analysis of rare spontaneous segregants has indicated that this locus is involved in the regulation of tumorigenicity and in the expression of the HeLa tumor-associated cell surface marker intestinal alkaline phosphatase (p75-IAP) in this system [10].

Analytical, diagnostic and therapeutic context of Akp3

• No difference in content of the major SLP protein (65 kDa) by Western blotting or immunocytochemistry was seen in stomach or colon of TNAP -/- vs. TNAP +/+ animals, but the content was only about half in the IAP-expressing small bowel [18].
• Only 20-34% of the intralumenal alkaline phosphatase (IAP) of the calf and pig is soluble and not within the sediment after centrifugation at 135,000 x g for 60 min. whereas the IAP of rodents is soluble in the range of 60-72% of the total IAP [19].
• These results suggest that the prodrug-converting system by membrane-bound IAP gene and EP prodrug is useful as the strong strategy of gene therapy for cancer treatment [2].
• To determine the chromosomal incorporation of membrane-bound IAP gene and AP activity in IAP gene-transduced cells (SNU638/IAP), we performed genomic PCR and AP activity analysis [2].
• In this report, we have analysed by Northern blots the pattern of expression of the IAP-related transcripts in the organs of young and ageing mice [20].

References