Getting Close: Insight into the Structure and Function of K11/K48-Branched Ubiquitin Chains

Baur, Regina; Rapé, Michael

doi:10.1016/j.str.2019.12.004

Cited by 14 publications

(25 citation statements)

References 10 publications

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“…Interestingly, the corresponding residue at this site in eukaryote ULPs is a Lys (Fig. 3A), which is functionally important and involved in the formation of poly‐ubiquitin chains in eukaryotes [23]. This indicates an evolutionary trajectory that could lead to fixation of Lys at this site in eukaryote ULPs in the context of haliophile to mesophile adaptation.…”

Section: Discussionmentioning

confidence: 99%

Halophilic to mesophilic adaptation of ubiquitin‐like proteins

Liu

et al. 2020

FEBS Letters

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Elucidating how proteins adapt from halophilic to mesophilic environments will enable a better understanding of protein evolution and folding. In this study, by directed evolution and site-directed mutagenesis of the halophilic ubiquitin-like protein (ULP) Samp2, we find that substitution of the prebiotic amino acid Asp31 by Gly is uniquely effective in the mesophilic adaptation of ULP. Sequence analysis shows that substitution of Asp/Glu in halophilic ULPs by Gly in mesophilic ULPs has higher occurrence than other substitutions, supporting the unique role of the substitution in the mesophilic adaptation of ULP. Molecular dynamic simulations indicate that the mesophilic adaptation might result from the effect of the substitution on the conformational flexibility of ULP.

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Section: Discussionmentioning

confidence: 99%

Halophilic to mesophilic adaptation of ubiquitin‐like proteins

Liu

et al. 2020

FEBS Letters

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“…Ubiquitin-proteasome system is involved in the degradation of more than 80% of proteins in cells [36]. K63-linked polyubiquitination is involved in signaling assemblies [32]. E3 ligases play a key role in the whole process of ubiquitination because of their specificity for substrates.…”

Section: Ubiquitination and Deubiquitinationmentioning

confidence: 99%

“…According to the number of ubiquitin attaching to one lysine residue in protein, ubiquitination is divided into monoubiquitination (single ubiquitin) and polyubiquitination (a chain of ubiquitin) [ 31 ]. In the polyubiquitination chain, ubiquitin can be attached via 7 lysine residues (K6, K11, K27, K29, K33, K48, and K63) or the first methionine (M1) [ 32 ]. Different types of ubiquitination lead to disparate fates of substrate proteins.…”

Section: Ubiquitination and Deubiquitinationmentioning

confidence: 99%

“…Different types of ubiquitination lead to disparate fates of substrate proteins. K48-linked polyubiquitination is the most widely studied type, which mainly labels proteins for 26S proteasome-mediated recognition and degradation [ 32 ]. K48-linked polyubiquitination also has proteasome independent functions, including regulation of signaling events and transcription, which are possibly determined by the length of the ubiquitin chain [ 33 – 35 ].…”

Section: Ubiquitination and Deubiquitinationmentioning

confidence: 99%

“…K48-linked polyubiquitination also has proteasome independent functions, including regulation of signaling events and transcription, which are possibly determined by the length of the ubiquitin chain [ 33 – 35 ]. K11-linked polyubiquitination is also associated with proteolysis [ 32 ]. Ubiquitin-proteasome system is involved in the degradation of more than 80% of proteins in cells [ 36 ].…”

Section: Ubiquitination and Deubiquitinationmentioning

confidence: 99%

See 2 more Smart Citations

The role of ubiquitination and deubiquitination in cancer metabolism

Sun¹,

Liu²,

Yang³

2020

Mol Cancer

277

178

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Metabolic reprogramming, including enhanced biosynthesis of macromolecules, altered energy metabolism, and maintenance of redox homeostasis, is considered a hallmark of cancer, sustaining cancer cell growth. Multiple signaling pathways, transcription factors and metabolic enzymes participate in the modulation of cancer metabolism and thus, metabolic reprogramming is a highly complex process. Recent studies have observed that ubiquitination and deubiquitination are involved in the regulation of metabolic reprogramming in cancer cells. As one of the most important type of post-translational modifications, ubiquitination is a multistep enzymatic process, involved in diverse cellular biological activities. Dysregulation of ubiquitination and deubiquitination contributes to various disease, including cancer. Here, we discuss the role of ubiquitination and deubiquitination in the regulation of cancer metabolism, which is aimed at highlighting the importance of this post-translational modification in metabolic reprogramming and supporting the development of new therapeutic approaches for cancer treatment.

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Deubiquitinase PSMD14 promotes ovarian cancer progression by decreasing enzymatic activity of PKM2

Sun

Liu

et al. 2021

Molecular Oncology

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Dysregulation of deubiquitination has been reported to contribute to carcinogenesis. However, the function and mechanism of deubiquitinating enzyme 26S proteasome non-ATPase regulatory subunit 14 (PSMD14) in the progression of ovarian cancer (OV), the deadliest gynecological cancer, still remains to be characterized. The present study demonstrated that PSMD14 was overexpressed in OV tissues and its higher levels correlated with a higher International Federation of Gynecology and Obstetrics (FIGO) stage in OV patients. A high level of PSMD14 expression was related to poor survival in OV patients. Knockdown and overexpression experiments elucidated that PSMD14 stimulated OV cell proliferation, invasion, and migration in vitro. Repression of PSMD14 suppressed OV tumor growth in vivo. PSMD14 inhibitor O-phenanthroline (OPA) effectively attenuated malignant behaviors of OV cells in vitro and OV tumor growth in vivo. Mechanistically, we uncovered that PSMD14 was involved in post-translational regulation of pyruvate kinase M2 isoform (PKM2). PSMD14 decreased K63-linked ubiquitination on PKM2, downregulated the ratio of PKM2 tetramers to dimers and monomers, and subsequently diminished pyruvate kinase activity and induced nuclear translocation of PKM2, contributing to aerobic glycolysis in OV cells. Collectively, our findings highlight the potential roles of PSMD14 as a biomarker and therapeutic candidate for OV.

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Getting Close: Insight into the Structure and Function of K11/K48-Branched Ubiquitin Chains

Cited by 14 publications

References 10 publications

Halophilic to mesophilic adaptation of ubiquitin‐like proteins

Halophilic to mesophilic adaptation of ubiquitin‐like proteins

The role of ubiquitination and deubiquitination in cancer metabolism

Deubiquitinase PSMD14 promotes ovarian cancer progression by decreasing enzymatic activity of PKM2

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