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Cisplatin induces t...
Cisplatin induces the proapoptotic conformation of Bak in a deltaMEKK1-dependent manner
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- Mandic, Aleksandra (författare)
- Karolinska Institutet
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- Viktorsson, Kristina (författare)
- Karolinska Institutet
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- Molin, Magnus (författare)
- Karolinska Institutet,Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
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- Akusjärvi, Göran (författare)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
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Eguchi, Hidetaka (författare)
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Hayashi, Shin-Ichi (författare)
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Toi, Masakazu (författare)
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- Hansson, Johan (författare)
- Karolinska Institutet
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- Linder, Stig (författare)
- Karolinska Institutet
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Shoshan, Maria C (författare)
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(creator_code:org_t)
- 2001
- 2001
- Engelska.
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Ingår i: Molecular and Cellular Biology. - 0270-7306 .- 1098-5549. ; 21:11, s. 3684-3691
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- In a panel of four human melanoma cell lines, equitoxic doses of cisplatin induced the proapoptotic conformation of the Bcl-2 family protein Bak prior to the execution phase of apoptosis. Because cisplatin-induced modulation of the related Bax protein was seen in only one cell line, a degree of specificity in the signal to Bak is indicated. Little is known about upstream regulation of Bak activity. In this study, we examined whether the apoptosis-specific pathway mediated by a kinase fragment of MEKK1 (DeltaMEKK1) is involved in the observed Bak modulation. We report that expression of a kinase-inactive fragment of MEKK1 (dominant negative MEKK [dnMEKK]) efficiently blocked cisplatin-induced modulation of Bak and cytochrome c release and consequently also reduced DEVDase activation and nuclear fragmentation. Accordingly, expression of a kinase-active MEKK1 fragment (dominant positive MEKK) was sufficient to induce modulation of Bak in three cell lines and to induce apoptosis in two of these. dnMEKK did not block cisplatin-induced c-Jun N-terminal kinase (JNK) activation, in agreement with a specifically proapoptotic role for the DeltaMEKK1 pathway. Finally, we show that reduction of Bak expression by antisense Bak reduced cisplatin-induced loss of mitochondrial integrity and caspase cleavage activity in breast cancer cell lines. In summary, we have identified Bak as a cisplatin-regulated component downstream in a proapoptotic, JNK-independent DeltaMEKK1 pathway.
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- MEDICINE
- MEDICIN
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- art (ämneskategori)
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Mandic, Aleksand ...
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Viktorsson, Kris ...
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Molin, Magnus
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Akusjärvi, Göran
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Eguchi, Hidetaka
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Hayashi, Shin-Ic ...
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visa fler...
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Toi, Masakazu
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Hansson, Johan
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Linder, Stig
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Shoshan, Maria C
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visa färre...
- Artiklar i publikationen
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Molecular and Ce ...
- Av lärosätet
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Uppsala universitet
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Karolinska Institutet