scholarly journals It's all about talking: two-way communication between proteasomal and lysosomal degradation pathways via ubiquitin

2016 ◽  
Vol 311 (2) ◽  
pp. C166-C178 ◽  
Author(s):  
Martina P. Liebl ◽  
Thorsten Hoppe
Keyword(s):  
Binding Proteins ◽  
Covalent Attachment ◽  
Special Importance ◽  
Heat Shock Factors ◽  
Substrate Selection ◽  
E3 Ligases ◽  
Age Related ◽  
General Decline ◽  
Ubiquitin Binding ◽  
Proteolytic Pathways

Selective degradation of proteins requires a fine-tuned coordination of the two major proteolytic pathways, the ubiquitin-proteasome system (UPS) and autophagy. Substrate selection and proteolytic activity are defined by a plethora of regulatory cofactors influencing each other. Both proteolytic pathways are initiated by ubiquitylation to mark substrate proteins for degradation, although the size and/or topology of the modification are different. In this context E3 ubiquitin ligases, ensuring the covalent attachment of activated ubiquitin to the substrate, are of special importance. The regulation of E3 ligase activity, competition between different E3 ligases for binding E2 conjugation enzymes and substrates, as well as their interplay with deubiquitylating enzymes (DUBs) represent key events in the cross talk between the UPS and autophagy. The coordination between both degradation routes is further influenced by heat shock factors and ubiquitin-binding proteins (UBPs) such as p97, p62, or optineurin. Mutations in enzymes and ubiquitin-binding proteins or a general decline of both proteolytic systems during aging result in accumulation of damaged and aggregated proteins. Thus further mechanistic understanding of how UPS and autophagy communicate might allow therapeutic intervention especially against age-related diseases.

Ubiquilins in the crosstalk among proteolytic pathways

2012 ◽  
Vol 393 (6) ◽  
pp. 441-447 ◽  
Author(s):  
Dong Yun Lee ◽  
Eric J. Brown
Keyword(s):  
Protein Degradation ◽  
Binding Proteins ◽  
Major Protein ◽  
Degradation Pathways ◽  
Cytosolic Proteins ◽  
Sequestosome 1 ◽  
Ubiquitin Binding ◽  
Proteolytic Pathways

Abstract Protein degradation occurs through several distinct proteolytic pathways for membrane and cytosolic proteins. There is evidence that these processes are linked and that crosstalk among these major protein degradation pathways occurs. Ubiquilins, a family of ubiquitin-binding proteins, are involved in all protein degradation pathways. This minireview provides an overview of ubiquilin function in protein degradation and contrasts it with sequestosome-1 (p62), a protein that also has been implicated in multiple proteolytic pathways.

scholarly journals Non-traditional Functions of Ubiquitin and Ubiquitin-binding Proteins

2003 ◽  
Vol 278 (38) ◽  
pp. 35857-35860 ◽  
Author(s):  
Joshua D. Schnell ◽  
Linda Hicke
Keyword(s):  
Binding Proteins ◽  
Ubiquitin Binding

Temporal and non-temporal processes in the elderly

2013 ◽  
Vol 24 (3) ◽  
pp. 191-199 ◽  
Author(s):  
Leah Fostick ◽  
Harvey Babkoff
Keyword(s):  
Temporal Resolution ◽  
Auditory Perception ◽  
Temporal Order ◽  
Temporal Order Judgment ◽  
Digit Span ◽  
Intensity Discrimination ◽  
Adult Intelligence Scale ◽  
Temporal Domain ◽  
Age Related ◽  
General Decline

Abstract Background: The present study examined whether the reported age-related decline in auditory temporal resolution is specific to the temporal domain or rather reflects a general decline in auditory perception, including the stimulus intensity domain. Methods: The performance of 89 healthy participants aged between 21 and 82 years with normal hearing was tested on a variety of psychophysical tasks, where discrimination was based either on the temporal or on the intensity domains. Stimulus levels for all tasks were 40 dB SL (corrected for threshold). Participants were also tested on two cognitive tasks: Wechsler Adult Intelligence Scale, Third Edition, matrices and digit span. Results: Findings indicate that age was significantly negatively correlated with performance on three of the temporal resolution tasks, namely, dichotic temporal-order judgment, spectral temporal-order judgment, and gap detection, but not on the intensity discrimination task, thus emphasizing the specificity of the age-related decline to the auditory temporal domain. Conclusions: The overall results suggest that age-related changes in auditory perception are specific to the temporal domain, even when controlling for hearing sensitivity and cognitive ability, and are not reflected in other aspects of non-temporal perception, such as intensity discrimination.

scholarly journals Regulation of ubiquitin-binding proteins by monoubiquitination

2006 ◽  
Vol 8 (2) ◽  
pp. 163-169 ◽  
Author(s):  
Daniela Hoeller ◽  
Nicola Crosetto ◽  
Blagoy Blagoev ◽  
Camilla Raiborg ◽  
Ritva Tikkanen ◽  
...  
Keyword(s):  
Binding Proteins ◽  
Ubiquitin Binding

scholarly journals The ARRE RING-Type E3 Ubiquitin Ligase Negatively Regulates Cuticular Wax Biosynthesis in Arabidopsis thaliana by Controlling ECERIFERUM1 and ECERIFERUM3 Protein Levels

2021 ◽  
Vol 12 ◽  
Author(s):  
Shuang Liu ◽  
Meixuezi Tong ◽  
Lifang Zhao ◽  
Xin Li ◽  
Ljerka Kunst
Keyword(s):  
Ubiquitin Ligase ◽  
Uv Light ◽  
E3 Ubiquitin Ligase ◽  
E3 Ligase ◽  
Cuticular Wax ◽  
26S Proteasome ◽  
Covalent Attachment ◽  
Wax Deposition ◽  
E3 Ligases ◽  
Ring Type

The outer epidermal cell walls of plant shoots are covered with a cuticle, a continuous lipid structure that provides protection from desiccation, UV light, pathogens, and insects. The cuticle is mostly composed of cutin and cuticular wax. Cuticular wax synthesis is synchronized with surface area expansion during plant development and is associated with plant responses to biotic and abiotic stresses. Cuticular wax deposition is tightly regulated by well-established transcriptional and post-transcriptional regulatory mechanisms, as well as post-translationally via the ubiquitin-26S proteasome system (UPS). The UPS is highly conserved in eukaryotes and involves the covalent attachment of polyubiquitin chains to the target protein by an E3 ligase, followed by the degradation of the modified protein by the 26S proteasome. A large number of E3 ligases are encoded in the Arabidopsis genome, but only a few have been implicated in the regulation of cuticular wax deposition. In this study, we have conducted an E3 ligase reverse genetic screen and identified a novel RING-type E3 ubiquitin ligase, AtARRE, which negatively regulates wax biosynthesis in Arabidopsis. Arabidopsis plants overexpressing AtARRE exhibit glossy stems and siliques, reduced fertility and fusion between aerial organs. Wax load and wax compositional analyses of AtARRE overexpressors showed that the alkane-forming branch of the wax biosynthetic pathway is affected. Co-expression of AtARRE and candidate target proteins involved in alkane formation in both Nicotiana benthamiana and stable Arabidopsis transgenic lines demonstrated that AtARRE controls the levels of wax biosynthetic enzymes ECERIFERUM1 (CER1) and ECERIFERUM3 (CER3). CER1 has also been confirmed to be a ubiquitination substrate of the AtARRE E3 ligase by an in vivo ubiquitination assay using a reconstituted Escherichia coli system. The AtARRE gene is expressed throughout the plant, with the highest expression detected in fully expanded rosette leaves and oldest stem internodes. AtARRE gene expression can also be induced by exposure to pathogens. These findings reveal that wax biosynthesis in mature plant tissues and in response to pathogen infection is controlled post-translationally.

scholarly journals Bayesian smoothed small-areas analysis of urban inequalities in fertility across 1999–2013

2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Brenda Biaani León-Gómez ◽  
Mercè Gotsens ◽  
Marc Marí-Dell’Olmo ◽  
Ma. Felicitas Domínguez-Berjón ◽  
Miguel Ángel Luque-Fernandez ◽  
...  
Keyword(s):  
Economic Crisis ◽  
Urban Areas ◽  
Socioeconomic Deprivation ◽  
Deprivation Index ◽  
Fertility Rates ◽  
Middle Income ◽  
Small Areas ◽  
Age Related ◽  
Low Middle Income Countries ◽  
General Decline

Abstract Background Since the 2008 economic crisis in Spain, overall fertility has continued to decrease, while urban inequalities have increased. There is a general lack of studies of fertility patterns in small-areas of Spanish cities. We explored the effects of the economic crisis on fertility during three time periods in urban settings in Spain. Methods We studied the distribution of fertility rates among women (15–49 years) from Spain and low-middle income countries (LIC) who were living in 13 Spanish cities. We mapped fertility and the MEDEA socioeconomic deprivation index in small-areas, and analyzed age-related trends in fertility rates. We performed an ecological regression analysis of fertility and the deprivation index in two pre-crisis periods (1999–2003 and 2004–2008) and one crisis period (2009–2013). Fertility rates were calculated and smoothed using the hierarchical Bayesian model (BYM). Results Higher fertility was generally associated with socioeconomic deprivation, with adjustment for the mothers’ age and nationality. While Spanish citizens tended to delay childbearing throughout the three study periods, fertility increased among Spanish adolescents from deprived urban areas during the economic crisis. There was a general decline in fertility among immigrants after the crisis, especially in southern cities. Overall, fertility appeared to be stable, with higher fertility in more deprived areas. Conclusion Increased unemployment and changes to government family policies may have contributed to delayed childbearing in Spain. For immigrants, more restrictive immigration policies may have played a crucial role in decreasing fertility rates. Reforming such policies will be key for better reproductive rights and improved fertility rates across all population cohorts in Spain.

scholarly journals Inhibition of DNA Binding by Differential Sumoylation of Heat Shock Factors

2006 ◽  
Vol 26 (3) ◽  
pp. 955-964 ◽  
Author(s):  
Julius Anckar ◽  
Ville Hietakangas ◽  
Konstantin Denessiouk ◽  
Dennis J. Thiele ◽  
Mark S. Johnson ◽  
...  
Keyword(s):  
Heat Shock ◽  
Dna Binding ◽  
Regulation Of Gene Expression ◽  
Binding Activity ◽  
Covalent Modification ◽  
Heat Shock Factors ◽  
Substrate Selection ◽  
Binding Domains ◽  
Dna Binding Activity ◽  
Specific Regulation

ABSTRACT Covalent modification of proteins by the small ubiquitin-related modifier SUMO regulates diverse biological functions. Sumoylation usually requires a consensus tetrapeptide, through which the binding of the SUMO-conjugating enzyme Ubc9 to the target protein is directed. However, additional specificity determinants are in many cases required. To gain insights into SUMO substrate selection, we have utilized the differential sumoylation of highly similar loop structures within the DNA-binding domains of heat shock transcription factor 1 (HSF1) and HSF2. Site-specific mutagenesis in combination with molecular modeling revealed that the sumoylation specificity is determined by several amino acids near the consensus site, which are likely to present the SUMO consensus motif to Ubc9. Importantly, we also demonstrate that sumoylation of the HSF2 loop impedes HSF2 DNA-binding activity, without affecting its oligomerization. Hence, SUMO modification of the HSF2 loop contributes to HSF-specific regulation of DNA binding and broadens the concept of sumoylation in the negative regulation of gene expression.

Sign in / Sign up

Export Citation Format

Share Document