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Review
. 2020 Oct 29;10(11):1493.
doi: 10.3390/biom10111493.

XIAP's Profile in Human Cancer

Affiliations
Review

XIAP's Profile in Human Cancer

Huailu Tu et al. Biomolecules. .

Abstract

XIAP, the X-linked inhibitor of apoptosis protein, regulates cell death signaling pathways through binding and inhibiting caspases. Mounting experimental research associated with XIAP has shown it to be a master regulator of cell death not only in apoptosis, but also in autophagy and necroptosis. As a vital decider on cell survival, XIAP is involved in the regulation of cancer initiation, promotion and progression. XIAP up-regulation occurs in many human diseases, resulting in a series of undesired effects such as raising the cellular tolerance to genetic lesions, inflammation and cytotoxicity. Hence, anti-tumor drugs targeting XIAP have become an important focus for cancer therapy research. RNA-XIAP interaction is a focus, which has enriched the general profile of XIAP regulation in human cancer. In this review, the basic functions of XIAP, its regulatory role in cancer, anti-XIAP drugs and recent findings about RNA-XIAP interactions are discussed.

Keywords: XIAP; apoptosis; cancer; non-coding RNA; therapeutics.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The structure of X-linked inhibitor of apoptosis protein (XIAP) homodimer. BIR: baculoviral IAP repeat. RING: RING (Really Interesting New Gene) finger doman.
Figure 2
Figure 2
XIAP and cellular function. XIAP mainly inhibits caspases-3/7/9 through binding, which blocks the pre-apoptotic pathways. SMAC, a mitochondrial protein, blocks XIAP’s cellular functions by occupying its binding sites. XIAP switches to necroptosis by RIPK3 and mixed lineage kinase domain like pseudokinase (MLKL), mediates autophagy by Mdm2 and p53 and regulates copper homeostasis by MURR1.
Figure 3
Figure 3
XIAP Signaling Pathways in Human Cancer. XIAP senses external signals through TGFβ and bone morphogenetic proteins (BMP) receptors. MNK activation and RPS3 (ribosomal protein S3) increase XIAP expression level. XIAP binds with TAB1, forming a XIAP-TAB1-TAB2-TAK1 complex, which further activates NF-κB and NF-κB-related downstream pathways. XIAP activates Smad signals which subsequently increases NF-κB and JNK activation, JNK activation alone can also switch on NF-κB pathway. Activated NF-κB and the FUS protein translocate into the nucleus, binding and initiating transcription of XIAP. Intranuclear XIAP binds to transcription factor Sp1 and E2F1, subsequently increasing transcription of miR-203 which further leads to MMP2 activation and invasion by inhibiting Src. Inhibition of miR-200a, stabilizing c-Myc and interacting with E2F1, XIAP facilitates anchorage-independent (AI) growth. XIAP promotes cell proliferation, viability and colony formation by blocking p62. Additionally, XIAP contributes to urothelial cell transformation through impairing p63α mRNA stability via miR-4295.

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References

    1. Duckett C.S., Nava V.E., Gedrich R.W., Clem R.J., Van Dongen J.L., Gilfillan M.C., Shiels H., Hardwick J.M., Thompson C.B. A conserved family of cellular genes related to the baculovirus iap gene and encoding apoptosis inhibitors. EMBO J. 1996;15:2685–2694. doi: 10.1002/j.1460-2075.1996.tb00629.x. - DOI - PMC - PubMed
    1. UniProtKB-Q6PIA0 (Q6PIA0_HUMAN) [(accessed on 29 October 2020)]; Available online: https://www.uniprot.org/uniprot/Q6PIA0//URL.
    1. Duckett C.S., Li F., Wang Y., Tomaselli K.J., Thompson C.B., Armstrong R.C. Human IAP-like protein regulates programmed cell death downstream of Bcl-xL and cytochrome c. Mol. Cell. Biol. 1998;18:608–615. doi: 10.1128/MCB.18.1.608. - DOI - PMC - PubMed
    1. Liston P., Roy N., Tamai K., Lefebvre C., Baird S., Cherton-Horvat G., Farahani R., McLean M., Ikeda J.E., MacKenzie A., et al. Suppression of apoptosis in mammalian cells by NAIP and a related family of IAP genes. Nature. 1996;379:349–353. doi: 10.1038/379349a0. - DOI - PubMed
    1. Sun C., Cai M., Gunasekera A.H., Meadows R.P., Wang H., Chen J., Zhang H., Wu W., Xu N., Ng S.C., et al. NMR structure and mutagenesis of the inhibitor-of-apoptosis protein XIAP. Nature. 1999;401:818–822. doi: 10.1038/44617. - DOI - PubMed

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