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A novel mitochondrial septin-like protein, ARTS, mediates apoptosis dependent on its P-loop motif

Nature Cell Biology volume 2, pages 915–921 (2000)Cite this article

Abstract

Here we describe a protein product of the human septin H5/PNUTL2/CDCrel2b gene, which we call ARTS (for apoptosis-related protein in the TGF-β signalling pathway). ARTS is expressed in many cells and acts to enhance cell death induced by TGF-β or, to a lesser extent, by other apoptotic agents. Unlike related septin gene products, ARTS is localized to mitochondria and translocates to the nucleus when apoptosis occurs. Mutation of the P-loop of ARTS abrogates its competence to activate caspase 3 and to induce apoptosis. Taken together, these observations expand the functional attributes of septins previously described as having roles in cytokinesis and cellular morphogenesis.

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Figure 1: ARTS represents a unique transcript of the H5 septin gene.
Figure 2: ARTS is detected as a 32K protein in cell lysates.
Figure 3: ARTS is essential for TGFβ-induced apoptosis.
Figure 4: ARTS-induced apoptosis correlates with caspase activation.
Figure 5: ARTS localizes to mitochondria.
Figure 6: Ligand-dependent translocation of ARTS from the mitochondria to the nucleus during apoptosis as shown by fluorescence microscopy.

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Acknowledgements

We thank M. Bloch for help and encouragement; D. Barzilai and Z. Ben-Ishai for support; Y. Ben-Neriah, A. Yaron, S. Gutkind and M. Zohar for discussions and advice; G. Yaniv and O. Binah for providing the neonatal ventricular myocytes; and N. Frumkin and A. H. Hsing for technical assistance. We thank D. B. Hales and K. H. Hales for providing the antiserum to recombinant murine StAR; the AU5–tag expression vector was provided by S. Gutkind; TGF-β receptor constructs were provided by J. Wrana and L. Attisano; and the p3TP–Lux construct was provided by J. Massagué. This work was supported by the Erna D. Leir Foundation for Research of Degenerative Brain Diseases, the National Alliance for Research of Schizophrenia and Depression, the National Parkinson Foundation Inc., the Israel Science Foundation funded by the Israel Academy of Sciences and Humanities (J.O.), and the NIH. H.S. is an investigator of the Howard Hughes Medical Institute.

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Author notes

  1. Robert J. Lechleider

    Present address: Department of Pharmacology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, Maryland, 20814-4799, USA

Authors and Affiliations

  1. Pathology Department, Rambam Medical Center, Haifa, Israel

    Sarit Larisch, Rona Lotan, Hedviga Kerner & Yossi Gottfried

  2. Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, 20892-5055, Maryland, USA

    Youngsuk Yi, Sarah Eimerl, W. Tony Parks, Mark P. de Caestecker, Robert J. Lechleider, Seong-Jin Kim & Anita B. Roberts

  3. Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, 20892-5055 , Maryland, USA

    Stephanie Birkey Reffey & Colin S. Duckett

  4. Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, Jerusalem , 91904, Israel

    Naomi Book-Melamed, Rina Timberg & Joseph Orly

  5. Cancer Center and Department of Pharmacology, Case Western Reserve University, 11001 Cedar Road, Cleveland, 44106, Ohio, USA

    David Danielpour

  6. Department of Biology Massachusetts Institute of Technology, Howard Hughes Medical Institute, 68-430, Cambridge, 02139, Massachusetts, USA

    Hermann Steller

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Correspondence to Anita B. Roberts.

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Larisch, S., Yi, Y., Lotan, R. et al. A novel mitochondrial septin-like protein, ARTS, mediates apoptosis dependent on its P-loop motif. Nat Cell Biol 2, 915–921 (2000). https://doi.org/10.1038/35046566

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