ArticleMolecular and cellular biology2001
Cisplatin induces the proapoptotic conformation of Bak in a deltaMEKK1-dependent manner.
Article in Molecular and cellular biology, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03261336 (A Phase II Study of Oral Calcitriol in Combination With Ketoconazole in Castration Resistant Prostate Cancer, Progressing Despite Primary ADT and Abiraterone), which is not on this map. Cited by 22 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase II Study of Oral Calcitriol in Combination With Ketoconazole in Castration Resistant Prostate Cancer, Progressing Despite Primary ADT and Abiraterone
Who cites it
22 citing papers in PubMed, 77 citations in OpenAlex.
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- Bak is a key molecule in apoptosis induced by methanol extracts of Codonopsis lanceolata and Tricholoma matsutake in HSC-2 human oral cancer cells.Oncology letters · 2012Article
- Chemosensitization by phenothiazines in human lung cancer cells: impaired resolution of γH2AX and increased oxidative stress elicit apoptosis associated with lysosomal expansion and intense vacuolation.Cell death & disease · 2011Article
- A novel biomarker harvesting nanotechnology identifies Bak as a candidate melanoma biomarker in serum.Experimental dermatology · 2011Article
- Heterodimerization of BAK and MCL-1 activated by detergent micelles.The Journal of biological chemistry · 2010Article
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- Identification of a novel topoisomerase inhibitor effective in cells overexpressing drug efflux transporters.PloS one · 2009Article
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- Akt-directed glucose metabolism can prevent Bax conformation change and promote growth factor-independent survival.Molecular and cellular biology · 2003Article
- The proteasome inhibitor PS-341 overcomes TRAIL resistance in Bax and caspase 9-negative or Bcl-xL overexpressing cells.Oncogene · 2003Article
- Bax and Bak can localize to the endoplasmic reticulum to initiate apoptosis.The Journal of cell biology · 2003Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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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