| Part one. The expression of iASPP in acute leukemias and its clinical significanceInhibitory member of the ASPP family (iASPP) is an evolutionarily conserved inhibitor of p53, and its expression is upregulated in human breast carcinomas expressing wild-type p53. To examine the role of iASPP in acute leukemia (AL), we analyzed iASPP mRNA expression in AL by semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR). PCR products were confirmed by restriction endonuclease BstX I digestion and sequencing analysis. The results showed that median levels of iASPP gene expression in cells of AL were significantly higher than those in cells from normal donors and AL patients in complete remission (CR) (p=0.019, 0.021, respectively). There was no significant difference between acute lymphocytic leukemia (ALL) cells and acute myeloid leukemia (AML) cells (p=0.593). The expression level of iASPP gene and overexpression in M3 and M4E0 was significantly lower than in other subtypes of AML. However, iASPP gene expression in AL cells was not associated with gender, age, initial white blood cell count or p53 type, but was associated with CD34 expression. The results of the present study suggest that iASPP gene overexpression may play an important role in the leukemogenesis and/or disease progression of AL. Part two. Identification of a 407 amino-acids form of iASPP and its interaction withp53iASPP at least includes two isoforms, one of iASPP/RAI(351 amino-acids, aa) and another of iASPP(828aa). RAJ was identified previously as a NF-kappaB subunit p65 (RelA) binding protein and inhibited its transcriptional activity. Further study demonstrated that iASPP/RAI shares extensively similar sequence with the C-terminal of ASPP1 and ASPP2. Moreover, iASPP/RAI is capable of binding to p53 and inhibits its ability to induce apoptosis. Accordingly, RAI also was referred to as iASPP (inhibitory member of the ASPP family). A novel isoform of human iASPP of...
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