Cell-fate determination by ubiquitin-dependent regulation of translation

Werner, Achim; Iwasaki, Shigeo; McGourty, Colleen A.; Medina-Ruiz, Sofía; Teerikorpi, Nia; Fedrigo, Indro; Ingolia, Nicholas T.; Rapé, Michael

doi:10.1038/nature14978

Cited by 156 publications

(199 citation statements)

References 36 publications

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“…2G). Indeed, TCOF1 has recently been shown to be downstream of rDNA transcription (24) as well as of PARP1 recruitment to rDNA (27). Notably, the mitochondrial membrane potential changes associated with TBP or POLR3A knockdown were not observed in PARP1-null cells (Fig.…”

Section: Ribosomal Defects Do Not Cause Mitochondrial Dysfunctionmentioning

confidence: 89%

Cockayne syndrome group A and B proteins converge on transcription-linked resolution of non-B DNA

Scheibye‐Knudsen

Tseng

Jensen

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Cockayne syndrome is a neurodegenerative accelerated aging disorder caused by mutations in the CSA or CSB genes. Although the pathogenesis of Cockayne syndrome has remained elusive, recent work implicates mitochondrial dysfunction in the disease progression. Here, we present evidence that loss of CSA or CSB in a neuroblastoma cell line converges on mitochondrial dysfunction caused by defects in ribosomal DNA transcription and activation of the DNA damage sensor poly-ADP ribose polymerase 1 (PARP1). Indeed, inhibition of ribosomal DNA transcription leads to mitochondrial dysfunction in a number of cell lines. Furthermore, machine-learning algorithms predict that diseases with defects in ribosomal DNA (rDNA) transcription have mitochondrial dysfunction, and, accordingly, this is found when factors involved in rDNA transcription are knocked down. Mechanistically, loss of CSA or CSB leads to polymerase stalling at non-B DNA in a neuroblastoma cell line, in particular at G-quadruplex structures, and recombinant CSB can melt G-quadruplex structures. Indeed, stabilization of G-quadruplex structures activates PARP1 and leads to accelerated aging in Caenorhabditis elegans. In conclusion, this work supports a role for impaired ribosomal DNA transcription in Cockayne syndrome and suggests that transcription-coupled resolution of secondary structures may be a mechanism to repress spurious activation of a DNA damage response.Cockayne syndrome | aging | polymerase I transcription | nucleolus | CSA | CSB

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Section: Ribosomal Defects Do Not Cause Mitochondrial Dysfunctionmentioning

confidence: 89%

Cockayne syndrome group A and B proteins converge on transcription-linked resolution of non-B DNA

Scheibye‐Knudsen

Tseng

Jensen

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…Cancer cells evolve rapidly, often leading to aneuploidy or a high mutational load, both of which increase the need for ubiquitin-dependent proteasomal or autophagosomal degradation (12,13). Similarly, ubiquitylation controls many important cell fate specification events during early development (14,15). These observations suggest that different ubiquitin levels may be critical in distinct cellular contexts, providing a potential explanation for the striking observation that gynecological cancers in particular may profit from stable repression of the UBB gene.…”

Section: Discussionmentioning

confidence: 99%

Ubiquitin levels: the next target against gynecological cancers?

Haakonsen¹,

Rapé²

2017

Journal of Clinical Investigation

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“…Protein purification, APC/C activity assays, immunoprecipitation, immunofluorescence microscopy, and CompPASS mass spectrometry were performed as described previously (12,14,54). Phosphatase assays were performed using the PP2A Immunoprecipitation Phosphatase Assay Kit (EMD Millipore) in accordance with the manufacturer's directions.…”

Section: Methodsmentioning

confidence: 99%

Control of APC/C-dependent ubiquitin chain elongation by reversible phosphorylation

Craney

Kelly

Jia

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Most metazoan E3 ligases contain a signature RING domain that promotes the transfer of ubiquitin from the active site of E2 conjugating enzymes to lysine residues in substrates. Although these RING-E3s depend on E2 enzymes for catalysis, how they turn on their E2s at the right time and place remains poorly understood. Here we report a phosphorylation-dependent mechanism that ensures timely activation of the E2 Ube2S by its RING-E3, the anaphase-promoting complex (APC/C); while phosphorylation of a specific serine residue in the APC/C coactivator Cdc20 prevents delivery of Ube2S to the APC/C, removal of this mark by PP2A B56 allows Ube2S to bind the APC/C and catalyze ubiquitin chain elongation. PP2AB56 also stabilizes kinetochore-microtubule attachments to shut off the spindle checkpoint, suggesting that cells regulate the E2-E3 interplay to coordinate ubiquitination with critical events during cell division.ubiquitin | anaphase-promoting complex | APC/C | Ube2S | phosphorylation

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Cell-fate determination by ubiquitin-dependent regulation of translation

Cited by 156 publications

References 36 publications

Cockayne syndrome group A and B proteins converge on transcription-linked resolution of non-B DNA

Cockayne syndrome group A and B proteins converge on transcription-linked resolution of non-B DNA

Ubiquitin levels: the next target against gynecological cancers?

Control of APC/C-dependent ubiquitin chain elongation by reversible phosphorylation

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