XIAP Monoubiquitylates Groucho/TLE to Promote Canonical Wnt Signaling

Hanson, Alison; Wallace, Heather A.; Freeman, Tanner J.; Beauchamp, R. Daniel; Lee, Laura A.; Lee, Ethan

doi:10.1016/j.molcel.2011.12.032

Cited by 72 publications

(81 citation statements)

References 40 publications

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“…The result is an increase in cytoplasmic and nuclear free ␤-catenin. Nuclear ␤-catenin displaces the corepressor TLE1 (transducin-like enhancer of split, or "Groucho" in Drosophila) from T-cell factor (TCF) and recruits XIAP to ubiquitinate TLE1 and target it for degradation (712). TCF and ␤-catenin can then promote transcription of multiple genes such as cyclin D1, myc, survivin, and IGF-I which facilitate proliferation, migration, and survival.…”

Section: Fibronectin Synthesis and Other Alterations Of The Ecm In Armentioning

confidence: 99%

Molecular Biology of Atherosclerosis

Hopkins

2013

Physiological Reviews

388

344

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At least 468 individual genes have been manipulated by molecular methods to study their effects on the initiation, promotion, and progression of atherosclerosis. Most clinicians and many investigators, even in related disciplines, find many of these genes and the related pathways entirely foreign. Medical schools generally do not attempt to incorporate the relevant molecular biology into their curriculum. A number of key signaling pathways are highly relevant to atherogenesis and are presented to provide a context for the gene manipulations summarized herein. The pathways include the following: the insulin receptor (and other receptor tyrosine kinases); Ras and MAPK activation; TNF-␣ and related family members leading to activation of NF-B; effects of reactive oxygen species (ROS) on signaling; endothelial adaptations to flow including G protein-coupled receptor (GPCR) and integrin-related signaling; activation of endothelial and other cells by modified lipoproteins; purinergic signaling; control of leukocyte adhesion to endothelium, migration, and further activation; foam cell formation; and macrophage and vascular smooth muscle cell signaling related to proliferation, efferocytosis, and apoptosis. This review is intended primarily as an introduction to these key signaling pathways. They have become the focus of modern atherosclerosis research and will undoubtedly provide a rich resource for future innovation toward intervention and prevention of the number one cause of death in the modern world.

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Section: Fibronectin Synthesis and Other Alterations Of The Ecm In Armentioning

confidence: 99%

Molecular Biology of Atherosclerosis

Hopkins

2013

Physiological Reviews

388

344

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“…WNT stimulation induces the monoubiquitylation of TLE3 by the E3 ligase XIAP and its consequent dissociation from TCF/LEF (Hanson et al . 2012). Ubiquitylation sites as well as DUBs for TLE3 remain to be elucidated.…”

Section: Transcriptional Regulation By Monoubiquitylation Of Nonhistomentioning

confidence: 99%

Protein monoubiquitylation: targets and diverse functions

Nakagawa

Nakayama

2015

Genes to Cells

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Ubiquitin is a 76‐amino acid protein whose conjugation to protein targets is a form of post‐translational modification. Protein ubiquitylation is characterized by the covalent attachment of the COOH‐terminal carboxyl group of ubiquitin to an amino group of the substrate protein. Given that the NH2‐terminal amino group is usually masked, internal lysine residues are most often targeted for ubiquitylation. Polyubiquitylation refers to the formation of a polyubiquitin chain on the substrate as a result of the ubiquitylation of conjugated ubiquitin. The structures of such polyubiquitin chains depend on the specific lysine residues of ubiquitin targeted for ubiquitylation. Most of the polyubiquitin chains other than those linked via lysine‐63 and methionine‐1 of ubiquitin are recognized by the proteasome and serve as a trigger for substrate degradation. In contrast, polyubiquitin chains linked via lysine‐63 and methionine‐1 serve as a binding platform for proteins that function in immune signal transduction or DNA repair. With the exception of a few targets such as histones, the functions of protein monoubiquitylation have remained less clear. However, recent proteomics analysis has shown that monoubiquitylation occurs more frequently than polyubiquitylation, and studies are beginning to provide insight into its biologically important functions. Here, we summarize recent findings on protein monoubiquitylation to provide an overview of the targets and molecular functions of this modification.

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“…At present, XIAP has been shown to be a protein of universal expression. It is expressed in various human tissues (12,13), but at low levels in normal cells and is increased in cancer cells (14–16). XIAP can inhibit tumor cell apoptosis and reduce tumor cell sensitivity, such as in ovarian cancer, glioma, prostate cancer, rectal cancer and childhood acute leukemia cells (17–20).…”

Section: Introductionmentioning

confidence: 99%

Effect of matrine combined with cisplatin on the expression of XIAP in human rhabdomyosarcoma RD cells

Xue

et al. 2016

Oncology Letters

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The combined effects of matrine (Mat) and cisplatin on the survival and apoptosis of rhabdomyosarcoma (RMS) RD cells, as well as the possible mechanism of the synergistic effect of Mat and cisplatin were investigated in the present study. RMS RD cells were divided and treated as follows: control group, 5 mg/l cisplatin group, Mat groups (0.5, 1.0 and 1.5 g/l), and Mat (0.5, 1.0 and 1.5 g/l) combined with 5 mg/l cisplatin groups. An MTT assay and flow cytometry were applied to detect the survival and apoptotic rates, respectively, while RT-PCR was applied to detect the expression levels of X-linked inhibitor of apoptosis protein (XIAP) mRNA in the RD cells of each group. The survival rates of RD cells in each experimental group were lower than in the control group, and the apoptotic rates were higher than those in the control group (P<0.05). An increase in drug concentrations led to the cell proliferation inhibitory and apoptotic rates of the single Mat groups increasing as a function of dose (pairwise comparison among the groups, P<0.05), while the proliferation inhibitory and apoptotic rates of Mat combined with the cisplatin groups under different concentration were significantly higher than those of the single Mat and single cisplatin groups under the same concentration (P<0.01). The expression levels of XIAP mRNA in the RD cells of each experimental group were lower than those in the control group (P<0.05). Additionally, the expression levels of XIAP mRNA in the group treated with Mat and cisplatin were significantly lower than those of the single cisplatin and single Mat groups (P<0.01). In conclusion, Mat and cisplatin are capable of inhibiting the proliferation of RD cells and inducing apoptosis by suppressing the XIAP mRNA expression levels.

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XIAP Monoubiquitylates Groucho/TLE to Promote Canonical Wnt Signaling

Cited by 72 publications

References 40 publications

Molecular Biology of Atherosclerosis

Molecular Biology of Atherosclerosis

Protein monoubiquitylation: targets and diverse functions

Effect of matrine combined with cisplatin on the expression of XIAP in human rhabdomyosarcoma RD cells

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