Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.3.1.108 (TAT)
 2,389 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Apoptin has been described to induce apoptosis in various human cancer cell lines, but not in normal cells, thus making it an interesting candidate for the development of novel therapeutic strategies. Apoptin was generated and cloned into several mammalian expression vectors. Transfection or microinjection of apoptin cDNA resulted in its expression, initially in the cytoplasm with a filamentous pattern. Subsequently, apoptin entered the nucleus and efficiently induced apoptosis in several cancer cell lines. Nuclear localization was shown to be required for induction of apoptosis. Apoptin expression level was found to be an important determinant of the efficiency of induction of apoptosis. Surprisingly, expression of apoptin or GFP-apoptin cDNA induced apoptosis in some normal cells. When fused to the HIV-TAT protein transduction domain and delivered as a protein, TAT-apoptin was transduced efficiently (>90%) into normal and tumour cells. However, TAT-apoptin remained in the cytoplasm and did not kill normal 6689 and 1BR3 fibroblasts. In contrast TAT-apoptin migrated from the cytoplasm to the nucleus of Saos-2 and HSC-3 cancer cells resulting in apoptosis after 24 h. This study shows that apoptin is a powerful apoptosis-inducing protein with a potential for cancer therapy.
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PMID:TAT-apoptin is efficiently delivered and induces apoptosis in cancer cells. 1469 60

HSCs are rare cells that have the unique ability to self-renew and differentiate into cells of all hematopoietic lineages. The lack of donors and current inability to rapidly and efficiently expand HSCs are roadblocks in the development of successful cell therapies. Thus, the challenge of ex vivo human HSC expansion remains a fertile and critically important area of investigation. Here, we show that either SALL4A- or SALL4B-transduced human HSCs obtained from the mobilized peripheral blood are capable of rapid and efficient expansion ex vivo by >10 000-fold for both CD34(+)/CD38(-) and CD34(+)/CD38(+) cells in the presence of appropriate cytokines. We found that these cells retained hematopoietic precursor cell immunophenotypes and morphology as well as normal in vitro or vivo potential for differentiation. The SALL4-mediated expansion was associated with enhanced stem cell engraftment and long-term repopulation capacity in vivo. Also, we demonstrated that constitutive expression of SALL4 inhibited granulocytic differentiation and permitted expansion of undifferentiated cells in 32D myeloid progenitors. Furthermore, a TAT-SALL4B fusion rapidly expanded CD34(+) cells, and it is thus feasible to translate this study into the clinical setting. Our findings provide a new avenue for investigating mechanisms of stem cell self-renewal and achieving clinically significant expansion of human HSCs.
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PMID:SALL4 is a robust stimulator for the expansion of hematopoietic stem cells. 2160 28