Regulation of inner nuclear membrane associated protein degradation

Koch, Bailey A.; Yu, Hong-Guo

doi:10.1080/19491034.2019.1644593

Cited by 13 publications

(12 citation statements)

References 108 publications

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“…Most likely, upon cell cycle exit, quality control mechanisms on pre-existing and newly synthesized LBR molecules, together with LBR transcriptional downregulation, contribute to decrease LBR INM-embedding, indirectly promoting LMNA-tether organization. However, whether LBR degradation occurs via the INM-associated degradation pathway or other pathways is unclear 32 , 61 .…”

Section: Discussionmentioning

confidence: 99%

Small heat-shock protein HSPB3 promotes myogenesis by regulating the lamin B receptor

et al. 2021

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One of the critical events that regulates muscle cell differentiation is the replacement of the lamin B receptor (LBR)-tether with the lamin A/C (LMNA)-tether to remodel transcription and induce differentiation-specific genes. Here, we report that localization and activity of the LBR-tether are crucially dependent on the muscle-specific chaperone HSPB3 and that depletion of HSPB3 prevents muscle cell differentiation. We further show that HSPB3 binds to LBR in the nucleoplasm and maintains it in a dynamic state, thus promoting the transcription of myogenic genes, including the genes to remodel the extracellular matrix. Remarkably, HSPB3 overexpression alone is sufficient to induce the differentiation of two human muscle cell lines, LHCNM2 cells, and rhabdomyosarcoma cells. We also show that mutant R116P-HSPB3 from a myopathy patient with chromatin alterations and muscle fiber disorganization, forms nuclear aggregates that immobilize LBR. We find that R116P-HSPB3 is unable to induce myoblast differentiation and instead activates the unfolded protein response. We propose that HSPB3 is a specialized chaperone engaged in muscle cell differentiation and that dysfunctional HSPB3 causes neuromuscular disease by deregulating LBR.

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Section: Discussionmentioning

confidence: 99%

Small heat-shock protein HSPB3 promotes myogenesis by regulating the lamin B receptor

et al. 2021

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“…RPN1 anchors proteasomes to the ER to form the endoplasmic reticulum-associated degradation (ERAD), less than 20 nm from the nucleus, whereas RPN9 anchors proteasomes to the nuclear pore complex (NPC) sites. Nuclear tethering of the proteasomes, for inner nuclear membrane-associated degradation (INMAD) [ 23 , 24 ], is mediated on two sites through RPN9 [ 21 ], on the or the nuclear core complex (NPC) via nuclear basket myosin-like protein (Mlp)—NPC interactome and directly via direct interaction with the Esc1p (Establishes silent chromatin 1p) [ 25 ].…”

Section: Proteasome Plasticitymentioning

confidence: 99%

Adaptation of Proteasomes and Lysosomes to Cellular Environments

Mebratu

Negasi

Dutta

et al. 2020

Cells

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Protein degradation is important for proper cellular physiology as it removes malfunctioning proteins or can provide a source for energy. Proteasomes and lysosomes, through the regulatory particles or adaptor proteins, respectively, recognize proteins destined for degradation. These systems have developed mechanisms to allow adaptation to the everchanging environment of the cell. While the complex recognition of proteins to be degraded is somewhat understood, the mechanisms that help switch the proteasomal regulatory particles or lysosomal adaptor proteins to adjust to the changing landscape of degrons, during infections or inflammation, still need extensive exploration. Therefore, this review is focused on describing the protein degradation systems and the possible sensors that may trigger the rapid adaptation of the protein degradation machinery.

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“…Protein degradation in the ER is highly dependent on the ubiquitin proteasome system and facilitates removal of both misfolded soluble and membrane proteins (43). Similarly, degradation of INM proteins can occur via biochemically similar pathways to ERassociated degradation of membrane proteins (44). Several branches of INM-associated degradation (INMAD) exist, each relying on a different E3 ubiquitin ligase to recognize and tag misfolded substrates through ubiquitination steps (45)(46)(47).…”

Section: Introductionmentioning

confidence: 99%

Nuclear envelope budding is a response to cellular stress

Panagaki

Croft

Keuenhof

et al. 2018

Preprint

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Eukaryotic cells are defined by the compartmentalization of the cytoplasm into organelles, the largest of which is the nucleus, which contains the cellular DNA. Transport into and out of the nucleus is highly regulated and is traditionally thought to occur solely through nuclear pores. However, a small number of papers has repeatedly shown vesicular budding from the nuclear envelopes in different organisms. We used electron microscopy to identify such nuclear envelope budding events in a human cell line, Caenorhabditis elegans worms, the two yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe and the parasitic protist Trypanosoma brucei. Progressing to electron tomography, the finer details of the 3D architecture of such budding events was revealed. We summarize all the organisms in which this mode of translocation over the nuclear envelope has been observed and conclude that this may be a fundamental, evolutionary conserved mechanism of transport inside eukaryotic cells.

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Regulation of inner nuclear membrane associated protein degradation

Cited by 13 publications

References 108 publications

Small heat-shock protein HSPB3 promotes myogenesis by regulating the lamin B receptor

Small heat-shock protein HSPB3 promotes myogenesis by regulating the lamin B receptor

Adaptation of Proteasomes and Lysosomes to Cellular Environments

Nuclear envelope budding is a response to cellular stress

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