Mortalin: Protein partners, biological impacts, pathological roles, and therapeutic opportunities
Mortalin (GRP75, HSPA9A), a heat shock protein (HSP), regulates a wide range of cellular processes, including cell survival, growth, and metabolism. The regulatory functions of mortalin are mediated through a diverse set of protein partners associated with different cellular compartments, which allo...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-02-01
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| Series: | Frontiers in Cell and Developmental Biology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2023.1028519/full |
| _version_ | 1797935375442771968 |
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| author | Niki Esfahanian Cole D. Knoblich Gaven A. Bowman Khosrow Rezvani |
| author_facet | Niki Esfahanian Cole D. Knoblich Gaven A. Bowman Khosrow Rezvani |
| author_sort | Niki Esfahanian |
| collection | DOAJ |
| description | Mortalin (GRP75, HSPA9A), a heat shock protein (HSP), regulates a wide range of cellular processes, including cell survival, growth, and metabolism. The regulatory functions of mortalin are mediated through a diverse set of protein partners associated with different cellular compartments, which allows mortalin to perform critical functions under physiological conditions, including mitochondrial protein quality control. However, alteration of mortalin’s activities, its abnormal subcellular compartmentalization, and its protein partners turn mortalin into a disease-driving protein in different pathological conditions, including cancers. Here, mortalin’s contributions to tumorigenic pathways are explained. Pathology information based on mortalin’s RNA expression extracted from The Cancer Genome Atlas (TCGA) transcriptomic database indicates that mortalin has an independent prognostic value in common tumors, including lung, breast, and colorectal cancer (CRC). Subsequently, the binding partners of mortalin reported in different cellular models, from yeast to mammalian cells, and its regulation by post-translational modifications are discussed. Finally, we focus on colorectal cancer and discuss how mortalin and its tumorigenic downstream protein targets are regulated by a ubiquitin-like protein through the 26S proteasomal degradation machinery. A broader understanding of the function of mortalin and its positive and negative regulation in the formation and progression of human diseases, particularly cancer, is essential for developing new strategies to treat a diverse set of human diseases critically associated with dysregulated mortalin. |
| first_indexed | 2024-04-10T18:13:27Z |
| format | Article |
| id | doaj.art-301481e696bf415a80cf8a3fd3130593 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-04-10T18:13:27Z |
| publishDate | 2023-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-301481e696bf415a80cf8a3fd31305932023-02-02T09:47:35ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2023-02-011110.3389/fcell.2023.10285191028519Mortalin: Protein partners, biological impacts, pathological roles, and therapeutic opportunitiesNiki EsfahanianCole D. KnoblichGaven A. BowmanKhosrow RezvaniMortalin (GRP75, HSPA9A), a heat shock protein (HSP), regulates a wide range of cellular processes, including cell survival, growth, and metabolism. The regulatory functions of mortalin are mediated through a diverse set of protein partners associated with different cellular compartments, which allows mortalin to perform critical functions under physiological conditions, including mitochondrial protein quality control. However, alteration of mortalin’s activities, its abnormal subcellular compartmentalization, and its protein partners turn mortalin into a disease-driving protein in different pathological conditions, including cancers. Here, mortalin’s contributions to tumorigenic pathways are explained. Pathology information based on mortalin’s RNA expression extracted from The Cancer Genome Atlas (TCGA) transcriptomic database indicates that mortalin has an independent prognostic value in common tumors, including lung, breast, and colorectal cancer (CRC). Subsequently, the binding partners of mortalin reported in different cellular models, from yeast to mammalian cells, and its regulation by post-translational modifications are discussed. Finally, we focus on colorectal cancer and discuss how mortalin and its tumorigenic downstream protein targets are regulated by a ubiquitin-like protein through the 26S proteasomal degradation machinery. A broader understanding of the function of mortalin and its positive and negative regulation in the formation and progression of human diseases, particularly cancer, is essential for developing new strategies to treat a diverse set of human diseases critically associated with dysregulated mortalin.https://www.frontiersin.org/articles/10.3389/fcell.2023.1028519/fullmortalin (HSPA9)cancerprotein partnerscellular localizationpost-translational modification (PTM) |
| spellingShingle | Niki Esfahanian Cole D. Knoblich Gaven A. Bowman Khosrow Rezvani Mortalin: Protein partners, biological impacts, pathological roles, and therapeutic opportunities Frontiers in Cell and Developmental Biology mortalin (HSPA9) cancer protein partners cellular localization post-translational modification (PTM) |
| title | Mortalin: Protein partners, biological impacts, pathological roles, and therapeutic opportunities |
| title_full | Mortalin: Protein partners, biological impacts, pathological roles, and therapeutic opportunities |
| title_fullStr | Mortalin: Protein partners, biological impacts, pathological roles, and therapeutic opportunities |
| title_full_unstemmed | Mortalin: Protein partners, biological impacts, pathological roles, and therapeutic opportunities |
| title_short | Mortalin: Protein partners, biological impacts, pathological roles, and therapeutic opportunities |
| title_sort | mortalin protein partners biological impacts pathological roles and therapeutic opportunities |
| topic | mortalin (HSPA9) cancer protein partners cellular localization post-translational modification (PTM) |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2023.1028519/full |
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