Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P62988 (Ubiquitin)
 4,326 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rhabdomyomas are the most common primary cardiac tumors in children, and have been shown to undergo spontaneous regression. The aim of our study was to investigate morphologically and immunohistochemically some mechanisms that may explain this clinical phenomenon. Eleven tumors from three term newborn girls who had physical and radiographic features pathognomonic of tuberous sclerosis were evaluated. Control specimens were left and right heart sections from five autopsies of age- and sex-matched patients who died of causes unrelated to the cardiovascular system. The tumors had been surgically excised from various regions in the heart, and all had similar "typical" histology. Histomorphologic evaluation with von Kossa and alizarin-red stains and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL) method were performed to evaluate cell calcifications, necrosis, and apoptosis. Ubiquitin immunohistochemical study was also conducted to evaluate intracytoplasmic protein degradation. In cardiac rhabdomyomas (CR), all myocytes with acidophilic cytoplasmic myofibrils showed strong intracytoplasmic ubiquitin immunoreactivity, compared with the occasional weak cytoplasmic and focal nuclear positivity in control heart sections. Calcified myocyte nuclei were commonly seen in CR tumoral and nontumoral rhabdomyocytes, whereas control nontumoral cardiac myocytes did not show any calcification. The incidence of TUNEL reactivity seen in CR (4.8 nuclei per 100 cardiac rhabdomyocyte nuclei) was higher than that seen in control heart sections (1.7 nuclei per 106 cardiac myocytes, P < 0.005). The data led us to conclude that the cytoplasmic contents in CR were degraded via the ubiquitin pathway, and from our observation of increased TUNEL positivity, the rate of cell death in CR appeared increased. These findings may explain, to some extent, the mechanism of tumor regression.
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PMID:Study of the regression process in cardiac rhabdomyomas. 1181 66

PI3K-Akt-FoxO-mTOR signaling is the central pathway controlling growth and metabolism in all cells. Ubiquitination of the protein kinase Akt prior to its phosphorylation is required for PI3K-Akt activity. Here, we found that the deubiquitinating (DUB) enzyme USP1 removes K63-linked polyubiquitin chains on Akt to restrict PI3K-Akt-FoxO signaling in mouse muscle during prolonged starvation. DUB screening platform identified USP1 as a direct DUB for Akt, and USP1 depletion in mouse muscle increased Akt ubiquitination, PI3K-Akt-FoxO signaling, and glucose uptake during fasting. Co-immunoprecipitation and mass spectrometry identified disabled homolog-2 (Dab2), the tuberous sclerosis complex TSC1/TSC2, and PHLPP1 as USP1 bound proteins. During starvation, Dab2 is essential for Akt recruitment to USP1-TSC1-PHLPP1 complex, and for PI3K-Akt-FoxO inhibition. Surprisingly, USP1 limits TSC1 levels to sustain mTOR-mediated basal protein synthesis rates and maintain its own protein levels. We propose that Dab2 recruits Akt to USP1-TSC1-PHLPP1 complex to efficiently terminate the transmission of growth signals when cellular energy level is low.
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PMID:USP1 deubiquitinates Akt to inhibit PI3K-Akt-FoxO signaling in muscle during prolonged starvation. 3213 36