Nuclear p62/SQSTM1 facilitates ubiquitin-independent proteasomal degradation of BMAL1.
Brain and muscle arnt-like protein 1(BMAL1) is a critical regulator of circadian rhythm. Although transcriptional regulation of BMAL1 has been extensively studied, the mechanisms governing the stability of BMAL1 at the protein level remain unclear. p62/SQSTM1 is a crucial factor in proteostasis regu...
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| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2025-07-01
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| Series: | PLoS Genetics |
| Online Access: | https://doi.org/10.1371/journal.pgen.1011794 |
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| author | Chenliang Zhang Quanyou Wu Huan Zhang Ruichen Liu Liping Li |
| author_facet | Chenliang Zhang Quanyou Wu Huan Zhang Ruichen Liu Liping Li |
| author_sort | Chenliang Zhang |
| collection | DOAJ |
| description | Brain and muscle arnt-like protein 1(BMAL1) is a critical regulator of circadian rhythm. Although transcriptional regulation of BMAL1 has been extensively studied, the mechanisms governing the stability of BMAL1 at the protein level remain unclear. p62/SQSTM1 is a crucial factor in proteostasis regulation and is involved in both autophagy and the ubiquitin-proteasome system. We demonstrated that p62 promotes proteasomal degradation of BMAL1 within the nucleus, independent of ubiquitination. Additional molecular analyses indicated that p62 functions as a receptor for the 20S proteasome, facilitating the recruitment of BMAL1 to the 20S proteasome for degradation. This mechanism is independent of recently identified p62-driven nuclear biomolecular condensates. We also revealed that remodeling the nuclear accumulation of p62 may represent a potential strategy for targeting BMAL1 to suppress tumor cell growth. In conclusion, our findings revealed a novel mechanism by which nuclear p62 regulates BMAL1 proteostasis. |
| format | Article |
| id | doaj-art-e1fcb0f66bdb4df69705c71d93ad2978 |
| institution | Kabale University |
| issn | 1553-7390 1553-7404 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj-art-e1fcb0f66bdb4df69705c71d93ad29782025-08-20T03:51:09ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042025-07-01217e101179410.1371/journal.pgen.1011794Nuclear p62/SQSTM1 facilitates ubiquitin-independent proteasomal degradation of BMAL1.Chenliang ZhangQuanyou WuHuan ZhangRuichen LiuLiping LiBrain and muscle arnt-like protein 1(BMAL1) is a critical regulator of circadian rhythm. Although transcriptional regulation of BMAL1 has been extensively studied, the mechanisms governing the stability of BMAL1 at the protein level remain unclear. p62/SQSTM1 is a crucial factor in proteostasis regulation and is involved in both autophagy and the ubiquitin-proteasome system. We demonstrated that p62 promotes proteasomal degradation of BMAL1 within the nucleus, independent of ubiquitination. Additional molecular analyses indicated that p62 functions as a receptor for the 20S proteasome, facilitating the recruitment of BMAL1 to the 20S proteasome for degradation. This mechanism is independent of recently identified p62-driven nuclear biomolecular condensates. We also revealed that remodeling the nuclear accumulation of p62 may represent a potential strategy for targeting BMAL1 to suppress tumor cell growth. In conclusion, our findings revealed a novel mechanism by which nuclear p62 regulates BMAL1 proteostasis.https://doi.org/10.1371/journal.pgen.1011794 |
| spellingShingle | Chenliang Zhang Quanyou Wu Huan Zhang Ruichen Liu Liping Li Nuclear p62/SQSTM1 facilitates ubiquitin-independent proteasomal degradation of BMAL1. PLoS Genetics |
| title | Nuclear p62/SQSTM1 facilitates ubiquitin-independent proteasomal degradation of BMAL1. |
| title_full | Nuclear p62/SQSTM1 facilitates ubiquitin-independent proteasomal degradation of BMAL1. |
| title_fullStr | Nuclear p62/SQSTM1 facilitates ubiquitin-independent proteasomal degradation of BMAL1. |
| title_full_unstemmed | Nuclear p62/SQSTM1 facilitates ubiquitin-independent proteasomal degradation of BMAL1. |
| title_short | Nuclear p62/SQSTM1 facilitates ubiquitin-independent proteasomal degradation of BMAL1. |
| title_sort | nuclear p62 sqstm1 facilitates ubiquitin independent proteasomal degradation of bmal1 |
| url | https://doi.org/10.1371/journal.pgen.1011794 |
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