Search

Your search keyword '"Tip110/SART3"' showing total 2 results
Start Over Descriptor "Tip110/SART3" Topic antigens, neoplasm
2 results on '"Tip110/SART3"'

1. Tip110/SART3 regulates IL-8 expression and predicts the clinical outcomes in melanoma.

Author

Timani KA, Győrffy B, Liu Y, Mohammad KS, and He JJ

Subjects
Female, Gene Expression Regulation, Neoplastic, Gene Knockdown Techniques, Humans, Interleukin-8 chemistry, Interleukin-8 metabolism, Male, Melanoma genetics, Melanoma pathology, Middle Aged, Neoplasm Invasiveness, Neoplasm Staging, Prognosis, RNA Stability, Antigens, Neoplasm genetics, Antigens, Neoplasm metabolism, Gene Expression Profiling methods, Interleukin-8 genetics, Melanoma metabolism, RNA-Binding Proteins genetics, RNA-Binding Proteins metabolism
Abstract

Tip110, an important regulator of several oncogenic proteins, was significantly downregulated in human metastatic melanoma cells exposed to a hypoxic condition. Therefore, in this study, we set to determine whether differential expression of Tip110 could be an important indicator for melanoma tumorigenesis and metastasis. We found that in melanoma, but not in other cancer types, Tip110 knockdown enhanced significant expression and secretion of IL-8 and melanoma cells invasions. This induction was further potentiated under hypoxia and by inflammatory cytokine and found independent of TNF-α autocrine signaling. We further showed that Tip110 knockdown-mediated IL-8 induction involved IL-8 mRNA stability. Furthermore, the transcriptomic profiling data and survival from 455 melanoma patients demonstrated that the correlation between Tip110 expression and the clinical outcomes in melanoma was stage-dependent. These findings uncover important roles of Tip110 in melanoma tumorigenesis and metastasis through regulation of IL-8 and hope to provide new clues for future therapeutic strategies.

Published
2018
Full Text
View/download PDF

2. Regulation of ubiquitin-proteasome system-mediated Tip110 protein degradation by USP15.

Author

Timani KA, Liu Y, Suvannasankha A, and He JJ

Subjects
Animals, Blotting, Western, Cell Proliferation, Cytoplasm metabolism, Female, HEK293 Cells, Humans, Immunoprecipitation, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, NIH 3T3 Cells, Proteolysis, RNA, Small Interfering genetics, RNA-Binding Proteins antagonists & inhibitors, Ubiquitination, Antigens, Neoplasm physiology, Proteasome Endopeptidase Complex metabolism, Protein Processing, Post-Translational, RNA-Binding Proteins physiology, Ubiquitin-Specific Proteases metabolism, Ubiquitins metabolism
Abstract

Tip110 is a nuclear protein and has been shown to function in tumor antigenicity, regulation of gene transcription, pre-mRNA splicing, stem cell proliferation and differentiation, and embryonic development. To characterize the in vivo functions of Tip110, a transgene cassette expressing human Tip110 protein (hTip110) was used to generate hTip110 transgenic (Tg) mice. Unexpectedly, only Tip110 mRNA but not Tip110 protein was expressed in Tg MEF and tissues. Treatment of Tg MEF with proteasome inhibitors led to detection of hTip110 protein, which prompted us to investigate the regulatory mechanisms of Tip110 degradation in mouse cells. We found that hTip110 was more sensitive to ubiquitin-proteasome system (UPS)-mediated protein degradation than mouse Tip110 (mTip110), likely resulting from more hTip110 ubiquitination. Using affinity chromatography and proteomics, we identified USP15, a deubiquitinating enzyme, to be associated with Tip110. Tip110 expression led to re-distribution of USP15 from the cytoplasm to the nucleus and complete co-localization of Tip110 with USP15 in the nucleus, whereas USP15 expression resulted in hTip110 deubiquitination. Interestingly, USP15 knockdown restored hTip110 protein expression in Tg MEF and USP15 expression had little effects. Taken together, these results provide insights into the regulatory mechanism of human Tip110 degradation by USP15., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Published
2014
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results