Next Article in Journal
Oral Administration of Alpha Linoleic Acid Rescues Aβ-Induced Glia-Mediated Neuroinflammation and Cognitive Dysfunction in C57BL/6N Mice
Next Article in Special Issue
Potency and Selectivity of SMAC/DIABLO Mimetics in Solid Tumor Therapy
Previous Article in Journal
“Circulating Tumor Cells: Finding Rare Events for a Huge Knowledge of Cancer Dissemination”
Previous Article in Special Issue
Future Therapeutic Directions for Smac-Mimetics
Review

Targeting XIAP for Promoting Cancer Cell Death—The Story of ARTS and SMAC

Laboratory of Cell Death and Cancer Research, Biology& Human Biology Departments, Faculty of Natural Sciences, University of Haifa, Haifa 3498838, Israel
*
Author to whom correspondence should be addressed.
Cells 2020, 9(3), 663; https://doi.org/10.3390/cells9030663
Received: 9 February 2020 / Revised: 4 March 2020 / Accepted: 6 March 2020 / Published: 9 March 2020
(This article belongs to the Special Issue Inhibitor of Apoptosis Proteins (IAPs) in Cancer Therapy)
Inhibitors of apoptosis (IAPs) are a family of proteins that regulate cell death and inflammation. XIAP (X-linked IAP) is the only family member that suppresses apoptosis by directly binding to and inhibiting caspases. On the other hand, cIAPs suppress the activation of the extrinsic apoptotic pathway by preventing the formation of pro-apoptotic signaling complexes. IAPs are negatively regulated by IAP-antagonist proteins such as Smac/Diablo and ARTS. ARTS can promote apoptosis by binding and degrading XIAP via the ubiquitin proteasome-system (UPS). Smac can induce the degradation of cIAPs but not XIAP. Many types of cancer overexpress IAPs, thus enabling tumor cells to evade apoptosis. Therefore, IAPs, and in particular XIAP, have become attractive targets for cancer therapy. In this review, we describe the differences in the mechanisms of action between Smac and ARTS, and we summarize efforts to develop cancer therapies based on mimicking Smac and ARTS. Several Smac-mimetic small molecules are currently under evaluation in clinical trials. Initial efforts to develop ARTS-mimetics resulted in a novel class of compounds, which bind and degrade XIAP but not cIAPs. Smac-mimetics can target tumors with high levels of cIAPs, whereas ARTS-mimetics are expected to be effective for cancers with high levels of XIAP. View Full-Text
Keywords: XIAP; cIAPs; ARTS; Smac; IAP antagonist; small molecules; apoptosis; cancer therapy XIAP; cIAPs; ARTS; Smac; IAP antagonist; small molecules; apoptosis; cancer therapy
Show Figures

Graphical abstract

MDPI and ACS Style

Abbas, R.; Larisch, S. Targeting XIAP for Promoting Cancer Cell Death—The Story of ARTS and SMAC. Cells 2020, 9, 663. https://doi.org/10.3390/cells9030663

AMA Style

Abbas R, Larisch S. Targeting XIAP for Promoting Cancer Cell Death—The Story of ARTS and SMAC. Cells. 2020; 9(3):663. https://doi.org/10.3390/cells9030663

Chicago/Turabian Style

Abbas, Ruqaia, and Sarit Larisch. 2020. "Targeting XIAP for Promoting Cancer Cell Death—The Story of ARTS and SMAC" Cells 9, no. 3: 663. https://doi.org/10.3390/cells9030663

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop