Project description:This SuperSeries is composed of the following subset Series: GSE26115: Regulation of transcription by HIP1 protein interactor (HIPPI) in HeLa cells GSE26116: Role of HIP1 in HIPPI mediated transcription regulation in HeLa cells Refer to individual Series
Project description:Nuclear entry of transcription factor HIPPI is mediated by its interacting partner Huntingtin Interacting Protein 1 (HIP1), a nuclear localization signal containing nucleo-cytoplasmic shuttling protein. In oredr to investigate the role of HIP1 in HIPPI mediated transcriptional regulation in cell, here we performed microarray experiments using stable HIP1 knocked down HeLa cells (Hip1Si) exogenously expressing Green fluorescent protein tagged HIPPI.
Project description:Genomic amplification of OTUD7B is frequently found across human cancers. But its role in tumorigenesis is poorly understood. Lysine‐specific demethylase 1 (LSD1) is known to execute epigenetic regulation by forming corepressor complex with CoREST/histone deacetylases (HDACs). However, the molecular mechanisms by which cells maintain LSD1/CoREST complex integrity are unknown. Here, it is reported that LSD1 protein undergoes K63‐linked polyubiquitination. OTUD7B is responsible for LSD1 deubiquitination at K226/277 residues, resulting in dynamic control of LSD1 binding partner specificity and cellular homeostasis. OTUD7B deficiency increases K63‐linked ubiquitination of LSD1, which disrupts LSD1/CoREST complex formation and targets LSD1 for p62‐mediated proteolysis. Consequently, OTUD7B deficiency impairs genome‐wide LSD1 occupancy and enhances the methylation of H3K4/H3K9, therefore profoundly impacting global gene expression and abrogating breast cancer metastasis. Moreover, physiological fluctuation of OTUD7B modulates cell cycle‐dependent LSD1 oscillation, ensuring the G1/S transition. Both OTUD7B and LSD1 proteins are overpresented in high‐grade or metastatic human breast cancer, while dysregulation of either protein is associated with poor survival and metastasis. Thus, OTUD7B plays a unique partner‐switching role in maintaining the integrity of LSD1/CoREST corepressor complex, LSD1 turnover, and breast cancer metastasis.