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Characterization of aggresome formation in choroid plexus carcinoma.
Protein misfolding is inevitable, 30% of newly synthesized polypeptides can end up misfolded, and such proteins are either refolded or eliminated by cellular quality control pathways. These pathways include the ubiquitin proteosome system and autophagy. In recent years, protein misfolding has been i...
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2017
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| _version_ | 1867613406864867328 |
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| access_status_str | Open Access |
| author | Nassar, Marwa Mohamed Ali |
| author_browse | Nassar, Marwa Mohamed Ali |
| author_facet | Nassar, Marwa Mohamed Ali |
| author_sort | Nassar, Marwa Mohamed Ali |
| collection | Thesis |
| dc_rights_str_mv | The author retains all rights with regard to copyright. The author certifies that written permission from the owner(s) of third-party copyrighted matter included in the thesis, dissertation, paper, or record of study has been obtained. The author further certifies that IRB approval has been obtained for this thesis, or that IRB approval is not necessary for this thesis. Insofar as this thesis, dissertation, paper, or record of study is an educational record as defined in the Family Educational Rights and Privacy Act (FERPA) (20 USC 1232g), the author has granted consent to disclosure of it to anyone who requests a copy. |
| description | Protein misfolding is inevitable, 30% of newly synthesized polypeptides can end up misfolded, and such proteins are either refolded or eliminated by cellular quality control pathways. These pathways include the ubiquitin proteosome system and autophagy. In recent years, protein misfolding has been implicated in the pathophysiology of many diseases such as diabetes, neurological disorders and cancer. Studies from our laboratory have shown that choroid plexus carcinoma tumors are characterized by the formation of aggresomes at the microtubules organizing centers (MTOC) in formalin fixed and paraffin embedded (FFPE) tumor tissues. This was further confirmed by the development of choroid plexus carcinoma cell line (CCHE-45) which was characterized by the constitutive formation of aggresomes at MTOC. Aggresome formation implies presence of toxic protein over load and/or defective autophagy. The role of autophagic flux in the removal of aggresomes was further investigated. CCHE-45 cells displayed an increase in both basal and induced autophagic flux. Furthermore, microtubule-associated protein light chain 3 A- variant 1 (LC3A-V1) expression was silenced by promoter methylation in these cells. Restoring LC3A-V1 resulted in the elimination of the aggresomes and the recruitment of Lysosomal-Associated Membrane Protein (LAMP2) independent from autophagosome formation. Based on these findings we suggest that quality control autophagy in CCHE-45 is mediated by LC3A in aggresomes clearance. We propose that perturbation in the autophagic pathway by the absence of LC3A expression leads to a failure in aggresome degradation thus overcoming misfolded protein overload. |
| format | Thesis |
| id | oai:fount.aucegypt.edu:etds-1019 |
| institution | American University in Cairo (Egypt) |
| last_indexed | 2026-06-10T12:35:38.861Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from AUC Knowledge Fountain — bepress |
| publishDate | 2017 |
| publishDateRange | 2017 |
| publishDateSort | 2017 |
| publisher | AUC Knowledge Fountain |
| publisherStr | AUC Knowledge Fountain |
| record_format | dspace |
| source_str | AUC Knowledge Fountain — bepress |
| spelling | oai:fount.aucegypt.edu:etds-1019 Characterization of aggresome formation in choroid plexus carcinoma. Nassar, Marwa Mohamed Ali Protein misfolding is inevitable, 30% of newly synthesized polypeptides can end up misfolded, and such proteins are either refolded or eliminated by cellular quality control pathways. These pathways include the ubiquitin proteosome system and autophagy. In recent years, protein misfolding has been implicated in the pathophysiology of many diseases such as diabetes, neurological disorders and cancer. Studies from our laboratory have shown that choroid plexus carcinoma tumors are characterized by the formation of aggresomes at the microtubules organizing centers (MTOC) in formalin fixed and paraffin embedded (FFPE) tumor tissues. This was further confirmed by the development of choroid plexus carcinoma cell line (CCHE-45) which was characterized by the constitutive formation of aggresomes at MTOC. Aggresome formation implies presence of toxic protein over load and/or defective autophagy. The role of autophagic flux in the removal of aggresomes was further investigated. CCHE-45 cells displayed an increase in both basal and induced autophagic flux. Furthermore, microtubule-associated protein light chain 3 A- variant 1 (LC3A-V1) expression was silenced by promoter methylation in these cells. Restoring LC3A-V1 resulted in the elimination of the aggresomes and the recruitment of Lysosomal-Associated Membrane Protein (LAMP2) independent from autophagosome formation. Based on these findings we suggest that quality control autophagy in CCHE-45 is mediated by LC3A in aggresomes clearance. We propose that perturbation in the autophagic pathway by the absence of LC3A expression leads to a failure in aggresome degradation thus overcoming misfolded protein overload. 2017-06-01T07:00:00Z dissertation application/pdf https://fount.aucegypt.edu/etds/20 https://fount.aucegypt.edu/context/etds/article/1019/viewcontent/final_20Dissertation_20Marwa_20Nassar_202017.pdf The author retains all rights with regard to copyright. The author certifies that written permission from the owner(s) of third-party copyrighted matter included in the thesis, dissertation, paper, or record of study has been obtained. The author further certifies that IRB approval has been obtained for this thesis, or that IRB approval is not necessary for this thesis. Insofar as this thesis, dissertation, paper, or record of study is an educational record as defined in the Family Educational Rights and Privacy Act (FERPA) (20 USC 1232g), the author has granted consent to disclosure of it to anyone who requests a copy. Theses and Dissertations AUC Knowledge Fountain Aggresomes Choroid plexus Carcinoma |
| spellingShingle | Aggresomes Choroid plexus Carcinoma Nassar, Marwa Mohamed Ali Characterization of aggresome formation in choroid plexus carcinoma. |
| title | Characterization of aggresome formation in choroid plexus carcinoma. |
| title_full | Characterization of aggresome formation in choroid plexus carcinoma. |
| title_fullStr | Characterization of aggresome formation in choroid plexus carcinoma. |
| title_full_unstemmed | Characterization of aggresome formation in choroid plexus carcinoma. |
| title_short | Characterization of aggresome formation in choroid plexus carcinoma. |
| title_sort | characterization of aggresome formation in choroid plexus carcinoma |
| topic | Aggresomes Choroid plexus Carcinoma |
| url | https://fount.aucegypt.edu/etds/20 https://fount.aucegypt.edu/context/etds/article/1019/viewcontent/final_20Dissertation_20Marwa_20Nassar_202017.pdf |
| work_keys_str_mv | AT nassarmarwamohamedali characterizationofaggresomeformationinchoroidplexuscarcinoma |