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Biomedical subjects

H M Noteborn

Publications and source records attributed to H M Noteborn.

2 recordsLinked to original sources

Apoptin.

Tumor cells are often characterized by the traithey are more resistant to apoptosis induced by e.g. cytotoxic agents than normal cells. Resistance to apoptosis induction can be a direct consequence of mutations in certain tumor-suppressor genes (p53) or of certain proto-oncogenes (Bcl-2). Therefore, new cancer therapies are under development to bypass the resistance to chemo- and radio-therapy of tumors. Apoptin acts independently of p53, is stimulated by Bcl-2 and is insensitive to BCR-ABL, which means that Apoptin can induce apoptosis in cases where present (chemo)-therapeutic agents, unfortunately, will fail. The fact that Apoptin induces apoptosis in human tumorigenic cells but not in normal diploid cells, implies that side-effects of Apoptin treatment are expected to be minor. In-vivo results with a first prototype of anti-tumor therapy based on expression of Apoptin indicate that Apoptin has low acute toxicity and is effective as an anti-tumor agent.

Animals↗

The xeroderma pigmentosum group B protein ERCC3 produced in the baculovirus system exhibits DNA helicase activity.

The XPB/ERCC3 gene corrects the nucleotide excision-repair defect in the human hereditary disease xeroderma pigmentosum group B and encodes the largest subunit of the basal transcription factor BTF2/TFIIH. The primary sequence of the XPB/ERCC3 protein features the hallmarks of seven helicase motifs found in many known and putative helicases or helicase-related proteins. Recently, the multiprotein BTF2/TFIIH complex has been found to be associated with DNA helicase activity. To explore the properties and functions of XPB/ERCC3, we have used the baculovirus/insect-cell expression system to produce recombinant protein. We report here the construction and analysis of recombinant baculovirus expressing XPB/ERCC3. The XPB/ERCC3 protein is synthesized at a relatively high level in baculovirus-infected insect cells. While the majority of XPB/ERCC3 end up in the insoluble fraction of insect cell lysates, a minor fraction of recombinant protein is present in soluble form which can be purified under native conditions. We have found that a DNA helicase activity is associated with the purified XPB/ERCC3 protein, suggesting that XPB/ERCC3 may function as a DNA helicase in local unwinding of DNA template both in the context of transcription and nucleotide excision repair.

Amino Acid Sequence↗