Enzymes of ubiquitination and deubiquitination

Neutzner, Melanie; Neutzner, Albert

doi:10.1042/bse0520037

Cited by 82 publications

(49 citation statements)

References 37 publications

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“…Ubiquitin proteins are first attached to the active cysteine of E1 and then transferred to the active cysteine of E2 by thioester linkage. E3 ligases mediate the transfer of ubiquitin on the active cysteine of E2 to a specific lysine of specific target proteins [3,4]. Depending on the types of ubiquitination, substrate proteins are destined for degradation or modulated their functions for numerous biological activities.…”

Section: Introductionmentioning

confidence: 99%

UBE2S is associated with malignant characteristics of breast cancer cells

Ayesha¹,

Hyodo²,

Asano³

et al. 2015

Tumor Biol.

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Ubiquitination is essential for various biological processes, such as signal transduction, intracellular trafficking, and protein degradation. Accumulating evidence has demonstrated that ubiquitination plays a crucial role in cancer development. In this report, we examine the expression and function of ubiquitin-conjugating enzyme E2S (UBE2S) in breast cancer. Immunohistochemical analysis revealed that UBE2S is highly expressed in breast cancer. The depletion of UBE2S by siRNA induced disruption of the actin cytoskeleton and focal adhesions. Interestingly, phosphorylation of FAK at Tyr397, which is important for the transduction of integrin-mediated signaling, was significantly reduced by UBE2S knockdown. We also show that UBE2S knockdown suppressed the malignant characteristics of breast cancer cells, such as migration, invasion, and anchorage-independent growth. Our results indicate that UBE2S could be a potential target for breast cancer treatment.

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Section: Introductionmentioning

confidence: 99%

UBE2S is associated with malignant characteristics of breast cancer cells

Ayesha¹,

Hyodo²,

Asano³

et al. 2015

Tumor Biol.

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“…12 In contrast, ubiquitin can be removed from proteins by deubiquitinating enzymes (DUBs). 13 Thus, ubiquitination is a dynamic cellular process that can quickly affect cellular protein levels and function.…”

mentioning

confidence: 99%

Comprehensive analysis of the ubiquitinome during oncogene-induced senescence in human fibroblasts

Bengsch

Tang

et al. 2015

Cell Cycle

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Oncogene-induced senescence (OIS) is an important tumor suppression mechanism preventing uncontrolled proliferation in response to aberrant oncogenic signaling. The profound functional and morphological remodelling of the senescent cell involves extensive changes. In particular, alterations in protein ubiquitination during senescence have not been systematically analyzed previously. Here, we report the first global ubiquitination profile of primary human cells undergoing senescence. We employed a well-characterized in vitro model of OIS, primary human fibroblasts expressing oncogenic RAS. To compare the ubiquitinome of RAS-induced OIS and controls, ubiquitinated peptides were enriched by immune affinity purification and subjected to liquid chromatography tandem mass spectrometry (LC-MS/MS). We identified 4,472 ubiquitination sites, with 397 sites significantly changed (>3 standard deviations) in senescent cells. In addition, we performed mass spectrometry analysis of total proteins in OIS and control cells to account for parallel changes in both protein abundance and ubiquitin levels that did not affect the percentage of ubiquitination of a given protein. Pathway analysis revealed that the OIS-induced ubiquitinome alterations mainly affected 3 signaling networks: eIF2 signaling, eIF4/p70S6K signaling, and mTOR signaling. Interestingly, the majority of the changed ubiquitinated proteins in these pathways belong to the translation machinery. This includes several translation initiation factors (eIF2C2, eIF2B4, eIF3I, eIF3L, eIF4A1) and elongation factors (eEF1G, eEF1A) as well as 40S (RPS4X, RPS7, RPS11 and RPS20) and 60S ribosomal subunits (RPL10, RPL11, RPL18 and RPL35a). In addition, we observed enriched ubiquitination of aminoacyl-tRNA ligases (isoleucyl-, glutamine-, and tyrosine-tRNA ligase), which provide the amino acid-loaded tRNAs for protein synthesis. These results suggest that ubiquitination affects key components of the translation machinery to regulate protein synthesis during OIS. Our results thus point toward ubiquitination as a hitherto unappreciated regulatory mechanism during OIS.

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“…The USP family includes more than 50 members in humans and is the largest family of DUBs. USPs are involved in tumor suppression, DNA repair, neural stem cell progenitor maintenance, immune response, viral replication, and epigenetic control (Katz et al, 2010;Nicholson and Suresh Kumar, 2011;Neutzner and Neutzner, 2012).…”

mentioning

confidence: 99%

Ubiquitin-Specific Proteases UBP12 and UBP13 Act in Circadian Clock and Photoperiodic Flowering Regulation in Arabidopsis

et al. 2013

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Protein ubiquitination is involved in most cellular processes. In Arabidopsis (Arabidopsis thaliana), ubiquitin-mediated protein degradation regulates the stability of key components of the circadian clock feedback loops and the photoperiodic flowering pathway. Here, we identified two ubiquitin-specific proteases, UBP12 and UBP13, involved in circadian clock and photoperiodic flowering regulation. Double mutants of ubp12 and ubp13 display pleiotropic phenotypes, including early flowering and short periodicity of circadian rhythms. In ubp12 ubp13 double mutants, CONSTANS (CO) transcript rises earlier than that of wild-type plants during the day, which leads to increased expression of FLOWERING LOCUS T. This, and analysis of ubp12 co mutants, indicates that UBP12 and UBP13 regulate photoperiodic flowering through a CO-dependent pathway. In addition, UBP12 and UBP13 regulate the circadian rhythm of clock genes, including LATE ELONGATED HYPOCOTYL, CIRCADIAN CLOCK ASSOCIATED1, and TIMING OF CAB EXPRESSION1. Furthermore, UBP12 and UBP13 are circadian controlled. Therefore, our work reveals a role for two deubiquitinases, UBP12 and UBP13, in the control of the circadian clock and photoperiodic flowering, which extends our understanding of ubiquitin in daylength measurement in higher plants.

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Enzymes of ubiquitination and deubiquitination

Cited by 82 publications

References 37 publications

UBE2S is associated with malignant characteristics of breast cancer cells

UBE2S is associated with malignant characteristics of breast cancer cells

Comprehensive analysis of the ubiquitinome during oncogene-induced senescence in human fibroblasts

Ubiquitin-Specific Proteases UBP12 and UBP13 Act in Circadian Clock and Photoperiodic Flowering Regulation in Arabidopsis

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