Progesterone receptor membrane component 1/Sigma-2 receptor associates with MAP1LC3B and promotes autophagy
| Autor: | Daret K. St. Clair, Woodrow Friend, Steven R. Schwarze, Ling Jin, Jinling Zhang, Shakeel U. R. Mir, Rolf J. Craven, Sumitra Miriyala |
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| Rok vydání: | 2013 |
| Předmět: |
Programmed cell death
Sigma-2 receptor UVRAG AMP-Activated Protein Kinases Biology BAG3 Tuberous Sclerosis Cell Line Tumor Sequestosome-1 Protein Autophagy Animals Humans Receptors sigma Molecular Biology PGRMC1 ATG16L1 Adaptor Proteins Signal Transducing Cell Proliferation Membrane Proteins Cell Biology Cell biology Biochemistry Proteolysis Receptors Progesterone Microtubule-Associated Proteins MAP1LC3B |
| Zdroj: | Autophagy. 9:1566-1578 |
| ISSN: | 1554-8635 1554-8627 |
| DOI: | 10.4161/auto.25889 |
| Popis: | Autophagy resembles a recycling process in which proteins, organelles, or regions of the cytoplasm are enveloped and degraded. We have found that two of the central autophagy proteins, MAP1LC3 (microtubule-associated protein 1 light chain 3, also described as LC3) and UVRAG (UV radiation resistance associated/UV radiation associated gene), complex with PGRMC1/S2R (progesterone receptor membrane component 1, also known as sigma-2 receptor). PGRMC1 is a cytochrome that is induced in cancer and is essential for tumor formation, invasion, and metastasis. Autophagy contributes to the turnover of long-lived and/or ubiquitinated proteins and the clearance of damaged organelles, and we have shown that PGRMC1 promotes both processes. Inhibition of PGRMC1 by RNAi or small molecule inhibitors causes autophagy substrates to increase and aberrant mitochondria to accumulate. We propose that this disruption of autophagy upon PGRMC1 inhibition increases AMPK activation, elevating the levels of TSC1 (tuberous sclerosis complex) and TSC2 and inactivating MTOR and RPS6KB/p70S6K, causing cleaved MAP1LC3B levels to increase. Thus, PGRMC1 binds to key components of the autophagy machinery and is required for the degradative activity of autophagy. |
| Databáze: | OpenAIRE |
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