Cul5-type Ubiquitin Ligase KLHDC1 Contributes to the Elimination of Truncated SELENOS Produced by Failed UGA/Sec Decoding

Okumura, Fumihiro; Fujiki, Yuha; Oki, Nodoka; Osaki, Kana; Nishikimi, Akihiko; Fukui, Yoshihiro; Nakatsukasa, Kunio; Kamura, Takumi

doi:10.1016/j.isci.2020.100970

Cited by 12 publications

(5 citation statements)

References 48 publications

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“…To date, six substrate receptors of multiprotein E3s have been found to recognize terminal degrons via β-propeller domains. C-degrons are recognized by Kelch β-propellers in KLHDC1, KLHDC2, KLHDC3, and KLHDC10, which function with either a CUL5-RBX2 or CUL2-RBX1 CRL catalytic core and by the WD40-repeat β-propellers in DCAF12, which functions with a CUL4-RBX1 CRL catalytic core ( Koren et al., 2018 ; Lin et al., 2018 ; Okumura et al., 2020 ). The WD40-repeat protein Gid11 is unique among GID substrate receptors in recognizing N-terminal Thr, and not Pro, but the basis for this specificity remains unknown ( Kong et al., 2021 ) ( Figure 4 A).…”

Section: Numerous N- and C-degron Pathwaysmentioning

confidence: 99%

How the ends signal the end: Regulation by E3 ubiquitin ligases recognizing protein termini

2022

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Section: Numerous N- and C-degron Pathwaysmentioning

confidence: 99%

How the ends signal the end: Regulation by E3 ubiquitin ligases recognizing protein termini

2022

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“…Each adaptor appears to recognise distinct G-end motifs, with KLHDC2 showing a strong preference for −GG, KLHDC3 targeting mainly −RG and −KG, and KLHDC10 recognising −AG, −WG and −PG. In addition, KLHDC1, a Cul5 substrate adaptor, can also recognise C-terminal −GG degrons [43].…”

Section: Gly/c-degron Pathwaysmentioning

confidence: 99%

Tying up loose ends: the N-degron and C-degron pathways of protein degradation

Timms

Koren

2020

Biochemical Society Transactions

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Selective protein degradation by the ubiquitin-proteasome system (UPS) is thought to be governed primarily by the recognition of specific motifs — degrons — present in substrate proteins. The ends of proteins — the N- and C-termini – have unique properties, and an important subset of protein–protein interactions involve the recognition of free termini. The first degrons to be discovered were located at the extreme N-terminus of proteins, a finding which initiated the study of the N-degron (formerly N-end rule) pathways, but only in the last few years has it emerged that a diverse set of C-degron pathways target analogous degron motifs located at the extreme C-terminus of proteins. In this minireview we summarise the N-degron and C-degron pathways currently known to operate in human cells, focussing primarily on those that have been discovered in recent years. In each case we describe the cellular machinery responsible for terminal degron recognition, and then consider some of the functional roles of terminal degron pathways. Altogether, a broad spectrum of E3 ubiquitin ligases mediate the recognition of a diverse array of terminal degron motifs; these degradative pathways have the potential to influence a wide variety of cellular functions.

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“…JAM3, an adhesion and transmigration regulatory element, is a novel tumor suppressor in colorectal cancer, and siRNA-mediated depletion of JAM3 increased cell invasion and migration [ 26 ]. KLHDC1 knockdown reduces endoplasmic reticulum stress-induced cell death, which is essential for maintaining reactive oxygen species levels and preventing cancer development [ 27 ]. AGRN is involved in the proliferation, migration and invasion of liver cancer cells by regulating focal adhesion integrity [ 28 ], and its expression is upregulated in cancers such as hepatocellular carcinoma, promoting EMT in primary tumors [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

RNA-seq reveals novel mechanistic targets of Livin in bladder cancer

et al. 2023

BMC Urol

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Background Bladder cancer is a very common malignancy with a high recurrence rate. The survival of patients with muscle-invasive bladder cancer is poor, and new therapies are needed. Livin has been reported to be upregulated in bladder cancer and influence the proliferation of cancer cells. Materials and methods The Livin gene in human bladder cancer cell line T24 was knocked out, and the differentially expressed genes were identified by RNA-seq and qPCR. Results Livin knockdown affects gene expression and has strong negative effects on some cancer-promoting pathways. Furthermore, combined with bladder cancer clinical sample data downloaded from TCGA and GEO, 2 co-up-regulated genes and 58 co-down-regulated genes were identified and validated, which were associated with cancer proliferation and invasion. Conclusion All these results suggest that Livin plays an important role in bladder cancer and could be a potential anticancer target in clinical therapy.

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Cul5-type Ubiquitin Ligase KLHDC1 Contributes to the Elimination of Truncated SELENOS Produced by Failed UGA/Sec Decoding

Cited by 12 publications

References 48 publications

How the ends signal the end: Regulation by E3 ubiquitin ligases recognizing protein termini

How the ends signal the end: Regulation by E3 ubiquitin ligases recognizing protein termini

Tying up loose ends: the N-degron and C-degron pathways of protein degradation

RNA-seq reveals novel mechanistic targets of Livin in bladder cancer

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