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Title:
UBL7 is indispensable for spermiogenesis through protecting critical factors from excessive degradation by proteasomes | Nature Communications
Description:
Spermiogenesis is a tightly regulated process to produce mature sperm cells. The ubiquitin-proteasome system (UPS) plays a crucial role in controlling protein half-life and is essential for spermiogenesis. Recently, proteins containing ubiquitin-like domains and ubiquitin-associated domains (UBL-UBA proteins) have emerged as novel regulators within the UPS. In this study, we demonstrate that UBL7, a testis-enriched UBL-UBA protein, is indispensable for sperm formation. Deficiency of UBL7 leads to severe malformations of both the sperm tail and head. Mechanistically, UBL7 interacts with the valosin-containing protein (VCP) complex and proteasomes, and shuttles substrates between them. Notably, UBL7 slows down the degradation rates of substrates involved in endoplasmic reticulum-associated degradation (ERAD) within cells. Through a two-step immunoprecipitation method, we identify several essential factors in spermatids that are protected by UBL7, including factors involved in the development of manchette (such as IFT140), head-tail coupling apparatus (such as SPATA20) and cytoplasmic droplets (such as HK1 and SLC2a3). In summary, our findings highlight UBL7 as a guardian that protects crucial factors from excessive degradation and thereby ensures successful spermiogenesis. Protein homeostasis is tightly regulated in developing sperm, which cease transcription during later stages of differentiation. Here they show that UBL7 can regulate the ubiquitin-proteasome system to safeguard key proteins during spermatogenesis.
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Keywords {🔍}
ubl, sperm, fig, pubmed, article, proteins, cells, google, scholar, protein, mice, cas, data, substrates, supplementary, degradation, spermatids, analysis, testis, cell, source, proteasomes, central, tubules, proteasome, vcp, bar, spermiogenesis, cds, testes, buffer, reduced, min, complex, staining, nature, file, antibody, mouse, incubated, biol, formation, germ, results, detected, ubconjugates, tail, provided, ubiquitin, identified,
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10 μm n-succinyl-leu-leu-val-tyr-7-amido-4-methylcoumarin human rad23b/psmd4/cd3δ/tyr/sod1/odc cdnas mouse ubl7/vcp/ufd1/npl4/ube4b/ub/psmd2/psmd4/adrm1 cdnas leu-leu-val-tyr-7-amido-4-methylcoumarin nature portfolio privacy policy boc-leu-gly-arg-amc multidisciplinary biomedical research international protein index research uncovers advertising 5 mm isopropyl β-d-thiogalactoside research design nature 477 nature social media midpiece-principal-piece connecting region36 reprints midpiece-principal-piece connecting region testis-specific endoplasmic reticulum author information authors bd facsaria fusion-ii thermo fisher scientific typical erad substrates—tyrosinase-c89r dominant x-linked juvenile promoting lys27-linked polyubiquitination specific pathogen-free conditions makes post-translational regulation supplementary movie 1 xbt x-ray film high-energy collisional dissociation testis-enriched ubl-uba protein enrich ubl7-interacting ub-conjugates open biol proteiniso® ni-nta resin midpiece-principalpiece connecting region anti-flag/myc/ha antibodies nano-esi ion source ubl-uba proteins exhibit 80 μg gst-ubl7-tube protein empty ha-tag vector tandem ubiquitin‐binding entities peer review file flag-tag vector serve head-neck connecting region midpiece-principal-piece bending controlling protein half-life ni-nta binding buffer including endoplasmic reticulum post-meiotic sperm production
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headline:UBL7 is indispensable for spermiogenesis through protecting critical factors from excessive degradation by proteasomes
description:Spermiogenesis is a tightly regulated process to produce mature sperm cells. The ubiquitin-proteasome system (UPS) plays a crucial role in controlling protein half-life and is essential for spermiogenesis. Recently, proteins containing ubiquitin-like domains and ubiquitin-associated domains (UBL-UBA proteins) have emerged as novel regulators within the UPS. In this study, we demonstrate that UBL7, a testis-enriched UBL-UBA protein, is indispensable for sperm formation. Deficiency of UBL7 leads to severe malformations of both the sperm tail and head. Mechanistically, UBL7 interacts with the valosin-containing protein (VCP) complex and proteasomes, and shuttles substrates between them. Notably, UBL7 slows down the degradation rates of substrates involved in endoplasmic reticulum-associated degradation (ERAD) within cells. Through a two-step immunoprecipitation method, we identify several essential factors in spermatids that are protected by UBL7, including factors involved in the development of manchette (such as IFT140), head-tail coupling apparatus (such as SPATA20) and cytoplasmic droplets (such as HK1 and SLC2a3). In summary, our findings highlight UBL7 as a guardian that protects crucial factors from excessive degradation and thereby ensures successful spermiogenesis. Protein homeostasis is tightly regulated in developing sperm, which cease transcription during later stages of differentiation. Here they show that UBL7 can regulate the ubiquitin-proteasome system to safeguard key proteins during spermatogenesis.
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headline:UBL7 is indispensable for spermiogenesis through protecting critical factors from excessive degradation by proteasomes
description:Spermiogenesis is a tightly regulated process to produce mature sperm cells. The ubiquitin-proteasome system (UPS) plays a crucial role in controlling protein half-life and is essential for spermiogenesis. Recently, proteins containing ubiquitin-like domains and ubiquitin-associated domains (UBL-UBA proteins) have emerged as novel regulators within the UPS. In this study, we demonstrate that UBL7, a testis-enriched UBL-UBA protein, is indispensable for sperm formation. Deficiency of UBL7 leads to severe malformations of both the sperm tail and head. Mechanistically, UBL7 interacts with the valosin-containing protein (VCP) complex and proteasomes, and shuttles substrates between them. Notably, UBL7 slows down the degradation rates of substrates involved in endoplasmic reticulum-associated degradation (ERAD) within cells. Through a two-step immunoprecipitation method, we identify several essential factors in spermatids that are protected by UBL7, including factors involved in the development of manchette (such as IFT140), head-tail coupling apparatus (such as SPATA20) and cytoplasmic droplets (such as HK1 and SLC2a3). In summary, our findings highlight UBL7 as a guardian that protects crucial factors from excessive degradation and thereby ensures successful spermiogenesis. Protein homeostasis is tightly regulated in developing sperm, which cease transcription during later stages of differentiation. Here they show that UBL7 can regulate the ubiquitin-proteasome system to safeguard key proteins during spermatogenesis.
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