Complex formation with monomeric α-tubulin and importin 13 fosters c-jun protein stability and is required for c-jun’s nuclear translocation and activity

Kappelmann-Fenzl M, Kuphal S, Krupar R, Schadendorf D, Umansky V, Vardimon L, Hellerbrand C, Boßerhoff AK (2019)

Publication Type: Journal article

Publication year: 2019

Journal

Cancers MDPI

Book Volume: 11

Article Number: 1806

Journal Issue: 11

DOI: 10.3390/cancers11111806

Abstract

Microtubules are highly dynamic structures, which consist of α-and β-tubulin heterodimers. They are essential for a number of cellular processes, including intracellular trafficking and mitosis. Tubulin-binding chemotherapeutics are used to treat different types of tumors, including malignant melanoma. The transcription factor c-Jun is a central driver of melanoma development and progression. Here, we identify the microtubule network as a main regulator of c-Jun activity. Monomeric α-tubulin fosters c-Jun protein stability by protein–protein interaction. In addition, this complex formation is necessary for c-Jun’s nuclear localization sequence binding to importin 13, and consequent nuclear import and activity of c-Jun. A reduction in monomeric α-tubulin levels by treatment with the chemotherapeutic paclitaxel resulted in a decline in the nuclear accumulation of c-Jun in melanoma cells in an experimental murine model and in patients’ tissues. These findings add important knowledge to the mechanism of the action of microtubule-targeting drugs and indicate the newly discovered regulation of c-Jun by the microtubule cytoskeleton as a novel therapeutic target for melanoma and potentially also other types of cancer.

Authors with CRIS profile

Melanie Kappelmann-Fenzl Lehrstuhl für Biochemie und Molekulare Medizin Silke Kuphal Lehrstuhl für Biochemie und Molekulare Medizin Claus Hellerbrand Professur für Biochemie und Molekulare Pathobiologie Anja Katrin Boßerhoff Lehrstuhl für Biochemie und Molekulare Medizin

Involved external institutions

Universitätsklinikum Schleswig-Holstein (UKSH) DE Germany (DE) Universität Duisburg-Essen (UDE) DE Germany (DE) Universitätsklinikum Mannheim DE Germany (DE) Tel Aviv University IL Israel (IL)

How to cite

APA:

Kappelmann-Fenzl, M., Kuphal, S., Krupar, R., Schadendorf, D., Umansky, V., Vardimon, L.,... Boßerhoff, A.K. (2019). Complex formation with monomeric α-tubulin and importin 13 fosters c-jun protein stability and is required for c-jun’s nuclear translocation and activity. Cancers, 11(11). https://dx.doi.org/10.3390/cancers11111806

MLA:

Kappelmann-Fenzl, Melanie, et al. "Complex formation with monomeric α-tubulin and importin 13 fosters c-jun protein stability and is required for c-jun’s nuclear translocation and activity." Cancers 11.11 (2019).

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