Oncogenic H-Ras up-regulates acid β-hexosaminidase by a mechanism dependent on the autophagy regulator TFEB.
The expression of constitutively active H-RasV12 oncogene has been described to induce proliferative arrest and premature senescence in many cell models. There are a number of studies indicating an association between senescence and lysosomal enzyme alterations, e.g. lysosomal β-galactosidase is the...
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2014
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oai:doaj.org-article:e35abbce096442dab9cf411f44a7e9632021-11-18T08:31:20ZOncogenic H-Ras up-regulates acid β-hexosaminidase by a mechanism dependent on the autophagy regulator TFEB.1932-620310.1371/journal.pone.0089485https://doaj.org/article/e35abbce096442dab9cf411f44a7e9632014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24586816/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203The expression of constitutively active H-RasV12 oncogene has been described to induce proliferative arrest and premature senescence in many cell models. There are a number of studies indicating an association between senescence and lysosomal enzyme alterations, e.g. lysosomal β-galactosidase is the most widely used biomarker to detect senescence in cultured cells and we previously reported that H-RasV12 up-regulates lysosomal glycohydrolases enzymatic activity in human fibroblasts. Here we investigated the molecular mechanisms underlying lysosomal glycohydrolase β-hexosaminidase up-regulation in human fibroblasts expressing the constitutively active H-RasV12. We demonstrated that H-Ras activation increases β-hexosaminidase expression and secretion by a Raf/extracellular signal-regulated protein kinase dependent pathway, through a mechanism that relies on the activity of the transcription factor EB (TFEB). Because of the pivotal role of TFEB in the regulation of lysosomal system biogenesis and function, our results suggest that this could be a general mechanism to enhance lysosomal enzymes activity during oncogene-induced senescence.Lorena UrbanelliAlessandro MaginiLuisa ErcolaniKrizia SaginiAlice PolchiBrunella TanciniAlessandro BrozziTatiana ArmeniGiovanni PrincipatoCarla EmilianiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 2, p e89485 (2014) |
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Medicine R Science Q Lorena Urbanelli Alessandro Magini Luisa Ercolani Krizia Sagini Alice Polchi Brunella Tancini Alessandro Brozzi Tatiana Armeni Giovanni Principato Carla Emiliani Oncogenic H-Ras up-regulates acid β-hexosaminidase by a mechanism dependent on the autophagy regulator TFEB. |
| description |
The expression of constitutively active H-RasV12 oncogene has been described to induce proliferative arrest and premature senescence in many cell models. There are a number of studies indicating an association between senescence and lysosomal enzyme alterations, e.g. lysosomal β-galactosidase is the most widely used biomarker to detect senescence in cultured cells and we previously reported that H-RasV12 up-regulates lysosomal glycohydrolases enzymatic activity in human fibroblasts. Here we investigated the molecular mechanisms underlying lysosomal glycohydrolase β-hexosaminidase up-regulation in human fibroblasts expressing the constitutively active H-RasV12. We demonstrated that H-Ras activation increases β-hexosaminidase expression and secretion by a Raf/extracellular signal-regulated protein kinase dependent pathway, through a mechanism that relies on the activity of the transcription factor EB (TFEB). Because of the pivotal role of TFEB in the regulation of lysosomal system biogenesis and function, our results suggest that this could be a general mechanism to enhance lysosomal enzymes activity during oncogene-induced senescence. |
| format |
article |
| author |
Lorena Urbanelli Alessandro Magini Luisa Ercolani Krizia Sagini Alice Polchi Brunella Tancini Alessandro Brozzi Tatiana Armeni Giovanni Principato Carla Emiliani |
| author_facet |
Lorena Urbanelli Alessandro Magini Luisa Ercolani Krizia Sagini Alice Polchi Brunella Tancini Alessandro Brozzi Tatiana Armeni Giovanni Principato Carla Emiliani |
| author_sort |
Lorena Urbanelli |
| title |
Oncogenic H-Ras up-regulates acid β-hexosaminidase by a mechanism dependent on the autophagy regulator TFEB. |
| title_short |
Oncogenic H-Ras up-regulates acid β-hexosaminidase by a mechanism dependent on the autophagy regulator TFEB. |
| title_full |
Oncogenic H-Ras up-regulates acid β-hexosaminidase by a mechanism dependent on the autophagy regulator TFEB. |
| title_fullStr |
Oncogenic H-Ras up-regulates acid β-hexosaminidase by a mechanism dependent on the autophagy regulator TFEB. |
| title_full_unstemmed |
Oncogenic H-Ras up-regulates acid β-hexosaminidase by a mechanism dependent on the autophagy regulator TFEB. |
| title_sort |
oncogenic h-ras up-regulates acid β-hexosaminidase by a mechanism dependent on the autophagy regulator tfeb. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2014 |
| url |
https://doaj.org/article/e35abbce096442dab9cf411f44a7e963 |
| work_keys_str_mv |
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| _version_ |
1718421715160137728 |