ArticlePloS one2012
Exosome-related multi-pass transmembrane protein TSAP6 is a target of rhomboid protease RHBDD1-induced proteolysis.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 40 citations in OpenAlex.
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- Genetic architecture of the murine red blood cell proteome reveals central role of hemoglobin beta cysteine 93 in maintaining redox balance.Cell genomics · 2026Article
- Holding Out for a Model: Rhomboid Superfamily in Vertebrate Development and Disease.Journal of cellular physiology · 2025Review
- Inflammatory response in gastrointestinal cancers: Overview of six transmembrane epithelial antigens of the prostate in pathophysiology and clinical implications.World journal of clinical oncology · 2024Review
- Protein cargo in extracellular vesicles as the key mediator in the progression of cancer.Cell communication and signaling : CCS · 2024Review
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- RHBDD1 promotes colorectal cancer metastasis through the Wnt signaling pathway and its downstream target ZEB1.Journal of experimental & clinical cancer research : CR · 2018Article
- Engineering mesenchymal stem cells to improve their exosome efficacy and yield for cell-free therapy.Journal of extracellular vesicles · 2018Review
- STEAP4: its emerging role in metabolism and homeostasis of cellular iron and copper.The Journal of endocrinology · 2017Review
- RHBDD1 upregulates EGFR via the AP-1 pathway in colorectal cancer.Oncotarget · 2017Article
- Rhomboid intramembrane protease RHBDL4 triggers ER-export and non-canonical secretion of membrane-anchored TGFα.Scientific reports · 2016Article
- Rhomboid domain containing 1 promotes colorectal cancer growth through activation of the EGFR signalling pathway.Nature communications · 2015Article
- A rhomboid protease gene deletion affects a novel oligosaccharide N-linked to the S-layer glycoprotein of Haloferax volcanii.The Journal of biological chemistry · 2014Article
- Rhomboid family gene expression profiling in breast normal tissue and tumor samples.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Article
- Structure and mechanism of rhomboid protease.The Journal of biological chemistry · 2013Review
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We have previously reported that rhomboid domain containing 1 (RHBDD1), a mammalian rhomboid protease highly expressed in the testis, can cleave the Bcl-2 protein Bik. In this study, we identified a multi-pass transmembrane protein, tumor suppressor activated pathway-6 (TSAP6) as a potential substrate of RHBDD1. RHBDD1 was found to induce the proteolysis of TSAP6 in a dose- and activity-dependent manner. The cleavage of TSAP6 was not restricted to its glycosylated form and occurred in three different regions. In addition, mass spectrometry and mutagenesis analyses both indicated that the major cleavage site laid in the C-terminal of the third transmembrane domain of TSAP6. A somatic cell knock-in approach was used to genetically inactivate the endogenous RHBDD1 in HCT116 and RKO colon cancer cells. Exosome secretion was significantly elevated when RHBDD1 was inactivated in the two cells lines. The increased exosome secretion was verfied through the detection of certain exosomal components, including Tsg101, Tf-R, FasL and Trail. In addition, the elevation of exosome secretion by RHBDD1 inactivation was reduced when TSAP6 was knocked down, indicating that the role of RHBDD1 in regulating exosomal trafficking is very likely to be TSAP6-dependent. We found that the increase in FasL and Trail increased exosome-induced apoptosis in Jurkat cells. Taken together, our findings suggest that RHBDD1 is involved in the regulation of a nonclassical exosomal secretion pathway through the restriction of TSAP6.
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