CRL4-DCAF12 Ubiquitin Ligase Controls MOV10 RNA Helicase during Spermatogenesis and T Cell Activation

Liďák, Tomáš; Baloghová, Nikol; Kor̆ínek, Vladimír; Sedláček, Radislav; Balounová, Jana; Kašpárek, Petr; Cermak, Laird S.

doi:10.3390/ijms22105394

Cited by 17 publications

(17 citation statements)

References 109 publications

(154 reference statements)

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“…A retroviral construct expressing eGFP-CENPB was a gift from Iain Cheeseman (pKG141-eGFP-CENPB; Addgene plasmid #69759). The cDNA library of the ubiquitin ligases was prepared as described previously ( Lidak et al, 2021 ).…”

Section: Methodsmentioning

confidence: 99%

FBXO38 Ubiquitin Ligase Controls Centromere Integrity via ZXDA/B Stability

Dibus

Kor̆ínek

Cermak

2022

Front. Cell Dev. Biol.

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Alterations in the gene encoding the E3 ubiquitin ligase substrate receptor FBXO38 have been associated with several diseases, including early-onset motor neuronopathy. However, the cellular processes affected by the enzymatic action of FBXO38 are not yet known. Here, we identify the zinc finger proteins ZXDA/B as its interaction partners. FBXO38 controls the stability of ZXDA/B proteins via ubiquitination and proteasome-dependent degradation. We show that ZXDA/B proteins associate with the centromeric protein CENP-B and that the interaction between ZXDA/B and FBXO38 or CENP-B is mutually exclusive. Functionally, ZXDA/B factors control the protein level of chromatin-associated CENP-B. Furthermore, their inappropriate stabilization leads to upregulation of CENP-A and CENP-B positive centromeric chromatin. Thus we demonstrate a previously unknown role of cullin-dependent protein degradation in the control of centromeric chromatin integrity.

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Section: Methodsmentioning

confidence: 99%

FBXO38 Ubiquitin Ligase Controls Centromere Integrity via ZXDA/B Stability

Dibus

Kor̆ínek

Cermak

2022

Front. Cell Dev. Biol.

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“…The motif is necessary and sufficient for ubiquitination of their hosts and was described as the canonical degron recognized by DCAF12 (Koren et al , 2018 ). Additional DCAF12 substrates were however later identified that do not harbor di‐Glu degrons (Cho et al , 2020 ; Lidak et al , 2021 ). DCAF12 downregulates MOV10, an RNA helicase involved in post‐transcriptional gene silencing, during T cell development and spermatogenesis (Lidak et al , 2021 ).…”

Section: Introductionmentioning

confidence: 99%

“…Additional DCAF12 substrates were however later identified that do not harbor di‐Glu degrons (Cho et al , 2020 ; Lidak et al , 2021 ). DCAF12 downregulates MOV10, an RNA helicase involved in post‐transcriptional gene silencing, during T cell development and spermatogenesis (Lidak et al , 2021 ). Recognition is mediated by the Glu‐Leu end of MOV10, and a range of proteins with noncanonical Glu‐Leu degrons appear to be substrates of DCAF12 (Koren et al , 2018 ; Lidak et al , 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Recognition of the CCT5 di‐Glu degron by CRL4^DCAF12 is dependent on TRiC assembly

et al. 2023

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Assembly Quality Control (AQC) E3 ubiquitin ligases target incomplete or incorrectly assembled protein complexes for degradation. The CUL4-RBX1-DDB1-DCAF12 (CRL4 DCAF12 ) E3 ligase preferentially ubiquitinates proteins that carry a C-terminal double glutamate (di-Glu) motif. Reported CRL4 DCAF12 di-Glu-containing substrates include CCT5, a subunit of the TRiC chaperonin. How DCAF12 engages its substrates and the functional relationship between CRL4 DCAF12 and CCT5/TRiC is currently unknown. Here, we present the cryo-EM structure of the DDB1-DCAF12-CCT5 complex at 2.8 A resolution. DCAF12 serves as a canonical WD40 DCAF substrate receptor and uses a positively charged pocket at the center of the b-propeller to bind the C-terminus of CCT5. DCAF12 specifically reads out the CCT5 di-Glu side chains, and contacts other visible degron amino acids through Van der Waals interactions. The CCT5 C-terminus is inaccessible in an assembled TRiC complex, and functional assays demonstrate that DCAF12 binds and ubiquitinates monomeric CCT5, but not CCT5 assembled into TRiC. Our biochemical and structural results suggest a previously unknown role for the CRL4 DCAF12 E3 ligase in overseeing the assembly of a key cellular complex.

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“…All three modules are weakly positively correlated with seroconversion. Key regulator DDB1 and CUL4 associated factor 12 ( DCAF12 ) is an ubiquitin ligase and controls spermatogenesis and T-cell activation ( Figure S15E ) (Lidak et al 2021). DCAF12 has also been identified as being differentially expressed between high and low responders after hepatitis B vaccination (Bartholomeus et al 2018).…”

Section: Resultsmentioning

confidence: 99%

Predicting seasonal influenza vaccine response using systemic gene expression profiling

Gresham

Forst²,

Chung³

et al. 2022

Preprint

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Seasonal influenza is a primary public health burden in the USA and globally. Annual vaccination programs are designed on the basis of circulating influenza viral strains. However, the effectiveness of the seasonal influenza vaccine is highly variable between seasons and among individuals. A number of factors are known to influence vaccination effectiveness including age, sex, and comorbidities. Here, we sought to determine whether whole blood gene expression profiling prior to vaccination is informative about pre-existing immunological status and the immunological response to vaccine. We performed whole transcriptome analysis using RNA sequencing (RNAseq) of whole blood samples obtained prior to vaccination from participants enrolled in an annual influenza vaccine trial. Serological status prior to vaccination and 28 days following vaccination was assessed using the hemagglutination inhibition assay (HAI) to define baseline immune status and the response to vaccination. We find evidence that genes with immunological functions are increased in expression in individuals with higher pre-existing immunity and in those individuals who mount a greater response to vaccination. Using a random forest model we find that this set of genes can be used to predict vaccine response with a performance similar to a model that incorporates physiological and prior vaccination status alone. Our study shows that increased expression of immunological genes, possibly reflecting greater plasmablast cell populations, prior to vaccination is associated with an enhanced response to vaccine. Furthermore, in the absence of physiological information and vaccination history, whole blood gene expression signatures are informative about the immunological response of an individual to seasonal influenza vaccination.

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CRL4-DCAF12 Ubiquitin Ligase Controls MOV10 RNA Helicase during Spermatogenesis and T Cell Activation

Cited by 17 publications

References 109 publications

FBXO38 Ubiquitin Ligase Controls Centromere Integrity via ZXDA/B Stability

FBXO38 Ubiquitin Ligase Controls Centromere Integrity via ZXDA/B Stability

Recognition of the CCT5 di‐Glu degron by CRL4^DCAF12 is dependent on TRiC assembly

Predicting seasonal influenza vaccine response using systemic gene expression profiling

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CRL4-DCAF12 Ubiquitin Ligase Controls MOV10 RNA Helicase during Spermatogenesis and T Cell Activation

Cited by 17 publications

References 109 publications

FBXO38 Ubiquitin Ligase Controls Centromere Integrity via ZXDA/B Stability

FBXO38 Ubiquitin Ligase Controls Centromere Integrity via ZXDA/B Stability

Recognition of the CCT5 di‐Glu degron by CRL4DCAF12 is dependent on TRiC assembly

Predicting seasonal influenza vaccine response using systemic gene expression profiling

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Recognition of the CCT5 di‐Glu degron by CRL4^DCAF12 is dependent on TRiC assembly