Disease relevance of CASP2

• Lymphomas were Ich1-L negative, except for T-cell-rich B-cell NHLs, and about half of the HD samples, in which Reed-Sternberg cells (RSC) were usually Ich1-L positive/CPP32 negative [1].
• T25 repeat in the 3' untranslated region of the CASP2 gene: a sensitive and specific marker for microsatellite instability in colorectal cancer [2].
• Immunohistochemical study revealed that CPP32 and ICH-1L were expressed weakly in the RA synovial lining cells compared with osteoarthritis (OA) synovial lining cells [3].
• Recent studies have shown that overexpression of the inactive forms of caspases CPP32 (caspase 3) and ICH-1 (caspase 2) is frequently observed in the blasts of patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) [4].
• Up-regulation of ICH-1L protein by thromboxane A2 antagonists enhances cisplatin-induced apoptosis in non-small-cell lung-cancer cell lines [5].

Psychiatry related information on CASP2

• Alteration of proteins regulating apoptosis, Bcl-2, Bcl-x, Bax, Bak, Bad, ICH-1 and CPP32, in Alzheimer's disease [6].

High impact information on CASP2

• We have solved the CARD structure of the RAIDD adaptor protein that recruits ICH-1/caspase-2 [7].
• We found that in its substrate preferences CED-3 was more similar to the mammalian CPP32 protease than to mammalian ICE or NEDD2/ICH-1 protease [8].
• Adenoviral vector-mediated transfer of active SREBP-2 also induced expression of the CASP-2 gene and the caspase-2 protein and increased the cholesterol and triacylglycerol cellular content [9].
• Exposure of several human cell lines to statins, lipid-lowering drugs that drive SREBP proteolytic activation, induced the CASP-2 gene to an extent similar to that for known targets of SREBP proteins [9].
• We show here that the 5'-flanking region of the human CASP-2 gene contains three functional response elements for sterol regulatory element binding proteins (SREBPs), proteins that mediate the transcriptional activation of genes involved in cholesterol, triacylglycerol, and fatty acid synthesis [9].

Biological context of CASP2

• Treatment of U937 and HL60 leukemic cells and HT29 colon carcinoma cells with the topoisomerase II inhibitor etoposide upregulates CASP-2 and CASP-3 genes in these cells before inducing their apoptosis [10].
• Neither CPP32 nor Ich1-L expression were correlated with intratumoral DNA fragmentation, as determined by the TUNEL assay [1].
• Apoptosis regulatory gene NEDD2 maps to human chromosome segment 7q34-35, a region frequently affected in haematological neoplasms [11].
• The differential expression of CPP32 and Ich1-L suggests that cysteine proteases differ in substrate specificities and carry out functions unrelated to apoptosis [1].
• Fold assignments for amino acid sequences of the CASP2 experiment [12].

Anatomical context of CASP2

• Cysteine protease CPP32, but not Ich1-L, is expressed in germinal center B cells and their neoplastic counterparts [1].
• In contrast, lymphoid organs displayed only weak Ich1-L expression, located in sinusal histiocytes and thymic epithelial cells [1].
• In particular, Jurkat T-lymphocytes treated with an irreversible caspase-2 inhibitor, benzyloxycarbonyl-Val-Asp-Val-Ala-Asp-fluoromethyl ketone (z-VDVAD-fmk), or stably transfected with pro-caspase-2 antisense (Casp-2/AS) are refractory to cytochrome c release stimulated by etoposide [13].
• Taken together, our results indicate that p53-induced, transactivation-independent apoptosis in Jurkat cells involves sequential activation of CPP32 or some other DEVD-sensitive caspase(s) and ICH-1, via a Fas-independent pathway [14].
• MATERIAL AND METHODS: The immunoreactivity of Bcl-2, Bax and ICH-1L were compared in ALS and control spinal cord motor neurons by immunohistochemical analysis and motor neurons with DNA fragmentation were identified by the TUNEL-method [15].

Associations of CASP2 with chemical compounds

• Ac-DEVD-CHO, an inhibitor of CPP32 activity, prevented the appearance of apoptotic cells, whereas the inhibitor of ICH-1L activity Z-VDVAD-FMK did not [16].
• Moreover, melatonin and flupirtine counteracted iron-ascorbate-induced ROS formation and decreased the ratio of mRNA for ICH-1L and ICH-1S [17].
• The levels of the mRNA transcripts for ICH-1L relative to those for ICH-1S were significantly decreased in cultures treated with 100 microM flupirtine or 100 microM melatonin when compared with levels in control cells [17].
• Treatment of RPE cells with 100 microM flupirtine gluconate for 72 hours caused an upregulation of the proto-oncogene protein Bcl-2 and a decrease in TIAR and ICH-1L proteins compared with that in control cells [17].
• Overexpression of ICH-1L and treatment with cisplatin might result in an increase in apoptosis in NSCLC cell lines [5].

Other interactions of CASP2

• No change is apparent between CASP2 and CASP3 (1998) [18].
• There was a clear improvement in alignment quality between CASP1 (1994) and CASP2 (1996) [18].
• Taken together, our results identify the human CASP-2 gene as a member of the SREBP-responsive gene battery that senses lipid levels in cells and raise the possibility that caspase-2 participates in the control of cholesterol and triacylglycerol levels [9].
• We have shown recently that the human CASP-2 gene, encoding procaspase-2, was under the positive control of SREBP-2 that transactivates several responsive elements in the promoter region [19].
• From observed changes in protein phosphatase 2A, CDC25 A, and caspase-2 precursor, a model for the promotion of cell cycle progression by ET-1 stimulation is proposed [20].

Analytical, diagnostic and therapeutic context of CASP2

• Western blot analysis demonstrated that untreated B lymphocytes expressed the proform of the ICE family members CPP32 and ICH1L, but no detectable ICE [21].
• By Northern blot analysis, cholangiocytes expressed the mRNA for three members of the ICE protease family: ICE, ICE/ CED-3 homologue-1 (ICH-1), and cysteine protease P-32 (CPP-32) [22].

References