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Start Over Author "Zheng JK" Publisher macmillan magazines ltd
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2. PTENα and PTENβ promote carcinogenesis through WDR5 and H3K4 trimethylation.

Author

Shen SM, Zhang C, Ge MK, Dong SS, Xia L, He P, Zhang N, Ji Y, Yang S, Yu Y, Zheng JK, Yu JX, Xia Q, and Chen GQ

Subjects
Animals, Carcinogenesis metabolism, Carcinogenesis pathology, Carcinoma, Hepatocellular metabolism, Carcinoma, Hepatocellular mortality, Carcinoma, Hepatocellular pathology, Cell Line, Tumor, Cell Movement, Cell Proliferation, Female, Histones metabolism, Humans, Intracellular Signaling Peptides and Proteins metabolism, Isoenzymes genetics, Isoenzymes metabolism, Liver metabolism, Liver pathology, Liver Neoplasms metabolism, Liver Neoplasms mortality, Liver Neoplasms pathology, Male, Mice, Mice, Nude, PTEN Phosphohydrolase metabolism, Proteolysis, Signal Transduction, Survival Analysis, Ubiquitin Thiolesterase genetics, Ubiquitin Thiolesterase metabolism, Ubiquitin-Protein Ligases genetics, Ubiquitin-Protein Ligases metabolism, Xenograft Model Antitumor Assays, beta-Transducin Repeat-Containing Proteins genetics, beta-Transducin Repeat-Containing Proteins metabolism, Carcinogenesis genetics, Carcinoma, Hepatocellular genetics, Gene Expression Regulation, Neoplastic, Histones genetics, Intracellular Signaling Peptides and Proteins genetics, Liver Neoplasms genetics, PTEN Phosphohydrolase genetics
Abstract

PTENα and PTENβ are two longer translational variants of phosphatase and tensin homolog (PTEN) messenger RNA. Their expressional regulations and functions in carcinogenesis remain largely unknown. Here, we demonstrate that, in contrast with the well-established tumour-suppressive role of canonical PTEN, PTENα and PTENβ promote tumourigenesis by directly interacting with the histone H3 lysine 4 (H3K4) presenter WDR5 to promote H3K4 trimethylation and maintain a tumour-promoting signature. We also show that USP9X and FBXW11 bind to the amino-terminal extensions of PTENα/β, and respectively deubiquitinate and ubiquitinate lysines 235 and 239 in PTENα to regulate PTENα/β stability. In accordance, USP9X promotes tumourigenesis and FBXW11 suppresses tumourigenesis through PTENα/β. Taken together, our results indicate that the Pten gene is a double-edged sword for carcinogenesis, and reinterpretation of the importance of the Pten gene in carcinogenesis is warranted.

Published
2019
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