אודות
Our lab focuses on investigating the molecular mechanisms of cell death, and how abnormal regulation of this process contributes to human diseases. We identified a mitochondrial pro-apoptotic protein termed ARTS (Sept4_i2) that is derived from the Sept4 septin gene by differential splicing. Over-expression of ARTS is sufficient to promote apoptosis in many cultured tumor cells. Conversely, the reduction of endogenous ARTS protein by anti-sense or shRNA methods can protect cells against various pro-apoptotic insults. This indicates that ARTS is important for induction of apoptosis in a wide variety of apoptosis paradigms. A central step for the execution of apoptosis is the activation of caspases, a family of enzymes that when activated bring about the demise of the cell. Caspases are regulated by both activators and inhibitors, such as IAPs (Inhibitor of Apoptosis Proteins). The best characterized member of this family is X-IAP (X-linked IAP). ARTS is located at the mitochondrial outer membrane (MOM) in living cells, but in response to pro-apoptotic stimuli it translocates to the cytosol. This permits ARTS to bind and inhibit XIAP, thereby initiating caspase activation and apoptosis.
פרסומים
- Corrigendum: Sept4/ARTS is required for stem cell apoptosis and tumor suppression (Genes Dev, (2010) 24, (2281-2293), 10.1101/gad.1970110, García-Fernández, M., Kissel, H., Brown, S., Gorenc, T., Schile, A. J., Rafii, S., Larisch, S. & Steller, H., 1 Dec 2025, In: Genes and Development. 39, 23-24, p. 1510 1 p.
- IFN-β and ARTS deficiency promote the generation of hyper-efferocytic Ly6C+ macrophages in resolving inflammation in male mice, Zeituni-Timor, O., Soboh, S., Zaid, A., Yaseen, H., Kumaran Satyanarayanan, S., Abu Zeid, M., Silberberg, E., Goswami, P., Schif-Zuck, S., Larisch, S. & Ariel, A., Dec 2025, In: Communications Biology. 8, 1, 1269.
- Chemical Tomography of Cancer Organoids and Cyto-Proteo-Genomic Development Stages Through Chemical Communication Signals, Maity, A., Maidantchik, V. D., Weidenfeld, K., Larisch, S., Barkan, D. & Haick, H., 26 Mar 2025, In: Advanced Materials. 37, 12, 2413017.
- ARTS and small-molecule ARTS mimetics upregulate p53 levels by promoting the degradation of XIAP, Abbas, R., Hartmann, O., Asiss, D. T., Abbas, R., Kagan, J., Kim, H. T., Oren, M., Diefenbacher, M., Orian, A. & Larisch, S., Aug 2024, In: Apoptosis. 29, 7-8, p. 1145-1160 16 p.
- Targeted Degradation of XIAP is Sufficient and Specific to Induce Apoptosis in MYCNoverexpressing High-risk Neuroblastoma, Choo, Z., Koh, X., Wong, M. R. E., Ashokan, R. M., Ahamed, N. S. B. A., Kang, C. B., Kuick, C. H., Chang, K. T. E., Larisch, S., Loh, A. H. P. & Chen, Z. X., Nov 2023, In: Cancer Research Communications. 3, 11, p. 2386-2399 14 p.
- Killing by degradation: Regulation of apoptosis by the ubiquitin-proteasome-system, Abbas, R. & Larisch, S., Dec 2021, In: Cells. 10, 12, 3465.
- p53 induces ARTS to promote mitochondrial apoptosis, Hao, Q., Chen, J., Liao, J., Huang, Y., Gan, Y., Larisch, S., Zeng, S. X., Lu, H. & Zhou, X., Feb 2021, In: Cell Death and Disease. 12, 2, 204.
- The “ARTS” of Cell Death in Service of Life: How Do We Force Cancer Cells to Commit Suicide?, Larisch, S., 2021, In: Frontiers for Young Minds. 9
- Inhibiting the inhibitors: Targeting anti-apoptotic proteins in cancer and therapy resistance, Shahar, N. & Larisch, S., Sep 2020, In: Drug Resistance Updates. 52, 100712.
- The pro-apoptotic ARTS protein induces neutrophil apoptosis, efferocytosis, and macrophage reprogramming to promote resolution of inflammation, Maimon, N., Zamir, Z. Z., Kalkar, P., Zeytuni-Timor, O., Schif-Zuck, S., Larisch, S. & Ariel, A., 1 Aug 2020, In: Apoptosis. 25, 7-8, p. 558-573 16 p.
- A small-molecule ARTS mimetic promotes apoptosis through degradation of both XIAP and Bcl-2, Mamriev, D., Abbas, R., Klingler, F. M., Kagan, J., Kfir, N., Donald, A., Weidenfeld, K., Sheppard, D. W., Barkan, D. & Larisch, S., 1 Jun 2020, In: Cell Death and Disease. 11, 6, 483.
- Targeting XIAP for promoting cancer cell death—the story of ARTS and SMAC, Abbas, R. & Larisch, S., Mar 2020, In: Cells. 9, 3, 663.
- Abstract GMM-045: Pax8 plays an essential role in high grade serious ovarian cancer via activation of mutant p53 and mislocalized p21, Ghannam, D., Jacob, E., Kakun, R., Wasserman, T., Korsensky, L., Sternfeld, O., Kagan, J., Bublik, D. R., Aviel-Ronen, S., Levanon, K., Sabo, E., Larisch, S., Oren, M., Hershkovitz, D. & Perets, R., 1 Nov 2019, In: Clinical Cancer Research. 25, 22_Supplement, p. GMM–045
- Another one bites the dust; ARTS enables degradation of Bcl-2 by XIAP, Mamriev, D. & Larisch, S., 4 Jul 2018, In: Molecular and Cellular Oncology. 5, 4, e1441630.
- International conference on Cell Death in Cancer and Toxicology 2018 (CDCT-2018), Ansari, K. M., Arany, P. R., Arama, E., Larisch, S., Birge, R. B. & Chandra, D., 28 Jun 2018, In: Cell Communication and Signaling. 16, 1, 33.
- PAX8 activates a p53-p21-dependent pro-proliferative effect in high grade serous ovarian carcinoma, Ghannam-Shahbari, D., Jacob, E., Kakun, R. R., Wasserman, T., Korsensky, L., Sternfeld, O., Kagan, J., Bublik, D. R., Aviel-Ronen, S., Levanon, K., Sabo, E., Larisch, S., Oren, M., Hershkovitz, D. & Perets, R., 1 Apr 2018, In: Oncogene. 37, 17, p. 2213-2224 12 p.
- Degradation of Bcl-2 by XIAP and ARTS Promotes Apoptosis, Edison, N., Curtz, Y., Paland, N., Mamriev, D., Chorubczyk, N., Haviv-Reingewertz, T., Kfir, N., Morgenstern, D., Kupervaser, M., Kagan, J., Kim, H. T. & Larisch, S., 10 Oct 2017, In: Cell Reports. 21, 2, p. 442-454 13 p.
- Parkin-mediated ubiquitination of mutant glucocerebrosidase leads to competition with its substrates PARIS and ARTS, Bendikov-Bar, I., Rapaport, D., Larisch, S. & Horowitz, M., 16 Jun 2014, In: Orphanet Journal of Rare Diseases. 9, 1, 86.
- Role of melanoma inhibitor of apoptosis (ML-IAP) protein, a member of the baculoviral IAP repeat (BIR) domain family, in the regulation of C-RAF kinase and cell migration, Oberoi-Khanuja, T. K., Karreman, C., Larisch, S., Rapp, U. R. & Rajalingam, K., 17 Aug 2012, In: Journal of Biological Chemistry. 287, 34, p. 28445-28455 11 p.
- Parkin promotes degradation of the mitochondrial pro-apoptotic ARTS protein, Kemeny, S., Dery, D., Loboda, Y., Rovner, M., Lev, T., Zuri, D., Finberg, J. P. M. & Larisch, S., 9 Jul 2012, In: PLOS ONE. 7, 7, e38837.
- Peptides mimicking the unique ARTS-XIAP binding site promote apoptotic cell death in cultured cancer cells, Edison, N., Reingewertz, T. H., Gottfried, Y., Lev, T., Zuri, D., Maniv, I., Carp, M. J., Shalev, G., Friedler, A. & Larisch, S., 1 May 2012, In: Clinical Cancer Research. 18, 9, p. 2569-2578 10 p.
- X-linked Inhibitor of Apoptosis Protein promotes the degradation of its antagonist, the pro-apoptotic ARTS protein, Bornstein, B., Edison, N., Gottfried, Y., Lev, T., Shekhtman, A., Gonen, H., Rajalingam, K. & Larisch, S., Mar 2012, In: International Journal of Biochemistry and Cell Biology. 44, 3, p. 489-495 7 p.
- The IAP-antagonist ARTS initiates caspase activation upstream of cytochrome C and SMACDiablo, Edison, N., Zuri, D., Maniv, I., Bornstein, B., Lev, T., Gottfried, Y., Kemeny, S., Garcia-Fernandez, M., Kagan, J. & Larisch, S., Feb 2012, In: Cell Death and Differentiation. 19, 2, p. 356-368 13 p.
- ARTS-based anticancer therapy: Taking aim at cancer stem cells, Elhasid, R. & Larisch, S., Oct 2011, In: Future Oncology. 7, 10, p. 1185-1194 10 p.
- Mechanism of the interaction between the intrinsically disordered C-terminus of the pro-apoptotic ARTS protein and the Bir3 domain of XIAP, Reingewertz, T. H., Shalev, D. E., Sukenik, S., Blatt, O., Rotem-Bamberger, S., Lebendiker, M., Larisch, S. & Friedler, A., 20 Sep 2011, In: PLOS ONE. 6, 9, e24655.
- ARTS binds to a distinct domain in XIAP-BIR3 and promotes apoptosis by a mechanism that is different from other IAP-antagonists, Bornstein, B., Gottfried, Y., Edison, N., Shekhtman, A., Lev, T., Glaser, F. & Larisch, S., Sep 2011, In: Apoptosis. 16, 9, p. 869-881 13 p.
- ARTS, the unusual septin: Structural and functional aspects, Mandel-Gutfreund, Y., Kosti, I. & Larisch, S., 1 Aug 2011, In: Biological Chemistry. 392, 8-9, p. 783-790 8 p.
- Sept4/ARTS is required for stem cell apoptosis and tumor suppression, García-Fernández, M., Kissel, H., Brown, S., Gorenc, T., Schile, A. J., Rafii, S., Larisch, S. & Steller, H., 15 Oct 2010, In: Genes and Development. 24, 20, p. 2282-2293 12 p.
- Mitochondrial Damage: A Target for New Therapeutic Horizons, Soustiel, J. F. & Larisch, S., Jan 2010, In: Neurotherapeutics. 7, 1, p. 13-21 9 p.
- Septins and Apoptosis, Carp, M. J. & Larisch, S., 24 Nov 2008, The Septins. John Wiley & Sons, Ltd, p. 281-293 13 p.
- The pro-apoptotic ARTS/Sept4 protein is significantly reduced in post-mortem brains from schizophrenic patients, Gottfried, Y., Rotem, A., Klein, E. & Larisch, S., Nov 2007, In: Schizophrenia Research. 96, 1-3, p. 257-266 10 p.
- Hydrogen peroxide predisposes neonatal rat ventricular myocytes to Fas-mediated apoptosis, Yaniv, G., Shilkrut, M., Larisch, S. & Binah, O., 28 Oct 2005, In: Biochemical and Biophysical Research Communications. 336, 3, p. 740-746 7 p.
- Regulation of the proapoptotic ARTS protein by ubiquitin-mediated degradation, Lotan, R., Rotem, A., Gonen, H., Finberg, J. P. M., Kemeny, S., Steller, H., Ciechanover, A. & Larisch, S., 8 Jul 2005, In: Journal of Biological Chemistry. 280, 27, p. 25802-25810 9 p.
- The Sept4 septin locus is required for sperm terminal differentiation in mice, Kissel, H., Georgescu, M. M., Larisch, S., Manova, K., Hunnicutt, G. R. & Steller, H., Mar 2005, In: Developmental Cell. 8, 3, p. 353-364 12 p.
- Erratum: Mitochondrial proapoptotic ARTS protein is lost in the majority of acute lymphoblastic leukemia patients (Oncogene (2004) 23 (5468-5475) doi:10.1038/sj.onc.1207725), Elhasid, R., Sahar, D., Merling, A., Zivony, Y., Rotem, A., Ben-Arush, M., Izraeli, S., Bercovich, D. & Larisch, S., 16 Dec 2004, In: Oncogene. 23, 58, p. 9450 1 p.
- Expression of the pro-apoptotic protein ARTS in astrocytic tumors: Correlation with malignancy grade and survival rate, Gottfried, Y., Voldavsky, E., Yodko, L., Sabo, E., Ben-Itzhak, O. & Larisch, S., 1 Dec 2004, In: Cancer. 101, 11, p. 2614-2621 8 p.
- The ARTS connection: Role of ARTS in apoptosis and cancer, Larisch, S., Aug 2004, In: Cell Cycle. 3, 8, p. 1019-1021 3 p.
- Mitochondrial pro-apoptotic ARTS protein is lost in the majority of acute lymphoblastic leukemia patients, Elhasid, R., Sahar, D., Merling, A., Zivony, Y., Rotem, A., Ben-Arush, M., Izraeli, S., Bercovich, D. & Larisch, S., 15 Jul 2004, In: Oncogene. 23, 32, p. 5468-5475 8 p.
- The mitochondrial ARTS protein promotes apoptosis through targeting XIAP, Gottfried, Y., Rotem, A., Lotan, R., Steller, H. & Larisch, S., 7 Apr 2004, In: EMBO Journal. 23, 7, p. 1627-1635 9 p.
- The Fas receptor - 1,4,5-IP3 cascade: A potential target for treating heart failure and arrhythmias, Binah, O., Shilkrut, M., Yaniv, G. & Larisch, S., 2004, In: Annals of the New York Academy of Sciences. 1015, p. 338-350 13 p.
- Tyrosine kinases inhibitors block Fas-mediated deleterious effects in normoxic and hypoxic ventricular myocytes, Shilkrut, M., Yaniv, G., Asleh, R., Levy, A. P., Larisch, S. & Binah, O., 1 Oct 2003, In: Journal of Molecular and Cellular Cardiology. 35, 10, p. 1229-1240 12 p.
- Hypoxia predisposes neonatal rat ventricular myocytes to apoptosis induced by activation of the Fas (CD95/Apo-1) receptor: Fas activation and apoptosis in hypoxic myocytes, Yaniv, G., Shilkrut, M., Lotan, R., Berke, G., Larisch, S. & Binah, O., 2002, In: Cardiovascular Research. 54, 3, p. 611-623 13 p.
- High glucose-induced replicative senescence: Point of no return and effect of telomerase, Blazer, S., Khankin, E., Segev, Y., Ofir, R., Yalon-Hacohen, M., Kra-Oz, Z., Gottfried, Y., Larisch, S. & Skorecki, K. L., 2002, In: Biochemical and Biophysical Research Communications. 296, 1, p. 93-101 9 p.
- Selective loss of the transforming growth factor-β apoptotic signaling pathway in mutant NRP-154 rat prostatic epithelial cells, Larisch-Bloch, S., Danielpour, D., Roche, N. S., Lotan, R., Hsing, A. Y., Kerner, H., Hajouj, T., Lechleider, R. J. & Roberts, A. B., Jan 2000, In: Cell Growth and Differentiation. 11, 1, p. 1-10 10 p.
- A novel mitochondrial septin-like protein, ARTS, mediates apoptosis dependent on its P-loop motif, Larisch, S., Yi, Y., Lotan, R., Kerner, H., Eimerl, S., Tony Parks, W., Gottfried, Y., Birkey Reffey, S., De Caestecker, M. P., Danielpour, D., Book-Melamed, N., Timberg, R., Duckett, C. S., Lechleider, R. J., Steller, H., Orly, J., Kim, S. J. & Roberts, A. B., 2000, In: Nature Cell Biology. 2, 12, p. 915-921 7 p.
- Characterization of functional domains within Smad4/DPC4, De Caestecker, M. P., Hemmati, P., Larisch-Bloch, S., Ajmera, R., Roberts, A. B. & Lechleider, R. J., 23 May 1997, In: Journal of Biological Chemistry. 272, 21, p. 13690-13696 7 p.
- LAK cells release a novel form of directly acting TGFβ tightly bound to a high molecular weight carrier(s), Larisch-Bloch, S. & Sulitzeanu, D., 1993, In: Growth Factors. 8, 3, p. 177-186 10 p.
- Degenerative changes in the A375 melanoma line induced by transforming growth factor beta 1, Larisch-Bloch, S., Yarom, R. & Sulitzeanu, D., Jul 1992, In: Immunology Letters. 33, 2, p. 151-156 6 p.
- A high molecular weight cytotoxic lymphokine in supernatants of lymphokine-activated killer cells cross-reacts with transforming growth factor beta, Larisch-Bloch, S., Sterman, B. & Sulitzeanu, D., Nov 1990, In: Immunology Letters. 26, 2, p. 189-192 4 p.
- Culture supernatants of lymphokine-activated killer (LAK) cells contain a high-molecular-weight cytotoxic lymphokine, Larisch-Bloch, S., Sterman, B., Weiss, D. & Sulitzeanu, D., Nov 1989, In: Immunology Letters. 23, 1, p. 27-30 4 p.