Analysis of the Yeast Peptidome and Comparison with the Human Peptidome

Dasgupta, Sayani; Yang, Ciyu; Castro, Leandro M.; Ferro, Emer S.; Moir, Robyn D.; Willis, Ian M.; Fricker, Lloyd D.

doi:10.1371/journal.pone.0163312

Cited by 35 publications

(63 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These studies also demonstrated that the overexpression of THOP1, which has been shown to be involved in the metabolism of specific intracellular peptides [53] and modulation of signal transduction of angiotensin II (AT1) and β-adrenergic GPCR in CHO and HEK293 cells. Recent studies in HEK293 cells showed that most of these intracellular peptides are generated by the proteasome, where additional intracellular peptide-generating peptidases also exist [52,[54][55][56].…”

Section: Brief Historical Perspective On Proteasome-derived Intracellmentioning

confidence: 99%

“…Different treatments and/or diseases modify the relative concentration of specific intracellular peptides present inside the cells and tissues, suggesting pathophysiological functions [51,54,55]. In challenge conditions, cells start accumulating or losing specific intracellular peptides that are biologically functional in such conditions.…”

Section: Brief Historical Perspective On Proteasome-derived Intracellmentioning

confidence: 99%

“…Intracellular peptides are mainly generated by proteasome [55,56,[60][61][62][63] and should function inside the cells, possibly regulating protein interactions [43,54,64,65]. However, a significant portion of intracellular peptides can be secreted [66], suggesting that they can also act on membrane receptors [67,68].…”

Section: Brief Historical Perspective On Proteasome-derived Intracellmentioning

confidence: 99%

See 2 more Smart Citations

Peptides from Natural or Rationally Designed Sources Can Be Used in Overweight, Obesity, and Type 2 Diabetes Therapies

et al. 2020

Self Cite

View full text Add to dashboard Cite

Overweight and obesity are among the most prominent health problems in the modern world, mostly because they are either associated with or increase the risk of other diseases such as type 2 diabetes, hypertension, and/or cancer. Most professional organizations define overweight and obesity according to individual body–mass index (BMI, weight in kilograms divided by height squared in meters). Overweight is defined as individuals with BMI from 25 to 29, and obesity as individuals with BMI ≥30. Obesity is the result of genetic, behavioral, environmental, physiological, social, and cultural factors that result in energy imbalance and promote excessive fat deposition. Despite all the knowledge concerning the pathophysiology of obesity, which is considered a disease, none of the existing treatments alone or in combination can normalize blood glucose concentration and prevent debilitating complications from obesity. This review discusses some new perspectives for overweight and obesity treatments, including the use of the new orally active cannabinoid peptide Pep19, the advantage of which is the absence of undesired central nervous system effects usually experienced with other cannabinoids.

show abstract

Section: Brief Historical Perspective On Proteasome-derived Intracellmentioning

confidence: 99%

Section: Brief Historical Perspective On Proteasome-derived Intracellmentioning

confidence: 99%

Section: Brief Historical Perspective On Proteasome-derived Intracellmentioning

confidence: 99%

See 1 more Smart Citation

Peptides from Natural or Rationally Designed Sources Can Be Used in Overweight, Obesity, and Type 2 Diabetes Therapies

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…Recently, our group developed a substrate-capture assay using a catalytically inactive form of thimet oligopeptidase (EC 3.4.24.15, EP24.15; THOP1) that allowed for the seminal identification of mammalian intracellular peptides, which are products of proteasome activity distinct from MHC-I antigens [9,10]. To date, multiple research groups have identified hundreds of novel intracellular peptides in human cell lines [11,12], human tissues [13,14], rodents [15,16], zebrafish [17], yeast [18], and plants [19,20]. THOP1 only hydrolyzes a restricted group of peptides in the optimal range of 8-12 amino acids in length [21][22][23], and has never been shown to degrade proteins, likely due to its catalytic site being deeply located in the bottom of a narrow channel [24,25].…”

Section: Introductionmentioning

confidence: 99%

The Relevance of Thimet Oligopeptidase in the Regulation of Energy Metabolism and Diet-Induced Obesity

et al. 2020

Self Cite

View full text Add to dashboard Cite

Thimet oligopeptidase (EC 3.4.24.15; EP24.15; THOP1) is a potential therapeutic target, as it plays key biological functions in processing biologically functional peptides. The structural conformation of THOP1 provides a unique restriction regarding substrate size, in that it only hydrolyzes peptides (optimally, those ranging from eight to 12 amino acids) and not proteins. The proteasome activity of hydrolyzing proteins releases a large number of intracellular peptides, providing THOP1 substrates within cells. The present study aimed to investigate the possible function of THOP1 in the development of diet-induced obesity (DIO) and insulin resistance by utilizing a murine model of hyperlipidic DIO with both C57BL6 wild-type (WT) and THOP1 null (THOP1−/−) mice. After 24 weeks of being fed a hyperlipidic diet (HD), THOP1−/− and WT mice ingested similar chow and calories; however, the THOP1−/− mice gained 75% less body weight and showed neither insulin resistance nor non-alcoholic fatty liver steatosis when compared to WT mice. THOP1−/− mice had increased adrenergic-stimulated adipose tissue lipolysis as well as a balanced level of expression of genes and microRNAs associated with energy metabolism, adipogenesis, or inflammation. Altogether, these differences converge to a healthy phenotype of THOP1−/− fed a HD. The molecular mechanism that links THOP1 to energy metabolism is suggested herein to involve intracellular peptides, of which the relative levels were identified to change in the adipose tissue of WT and THOP1−/− mice. Intracellular peptides were observed by molecular modeling to interact with both pre-miR-143 and pre-miR-222, suggesting a possible novel regulatory mechanism for gene expression. Therefore, we successfully demonstrated the previously anticipated relevance of THOP1 in energy metabolism regulation. It was suggested that intracellular peptides were responsible for mediating the phenotypic differences that are described herein by a yet unknown mechanism of action.

show abstract

“…For example, the formation of AtRALF1 and AtRALF23 peptides depends on precursor cleavage by subtilisin‐like proteinase S1P/SBT6.1 (serine‐type), and phytaspases (aspartic‐type) were shown to cleave prosystemin in tomato . In addition, proteasomes, which have caspase‐like, trypsin‐like, and chymotrypsin‐like activities, can be responsible for the generation of peptide pools in animal cells . However, it is not known whether proteasomes influence peptide pools in plant cells and secretomes.…”

Section: Introductionmentioning

confidence: 99%

Salicylic acid influences the protease activity and posttranslation modifications of the secreted peptides in the moss Physcomitrella patens

Filippova

Lyapina

Kirov

et al. 2018

Journal of Peptide Science

View full text Add to dashboard Cite

Plant secretome comprises dozens of secreted proteins. However, little is known about the composition of the whole secreted peptide pools and the proteases responsible for the generation of the peptide pools. The majority of studies focus on target detection and characterization of specific plant peptide hormones. In this study, we performed a comprehensive analysis of the whole extracellular peptidome, using moss Physcomitrella patens as a model. Hundreds of modified and unmodified endogenous peptides that originated from functional and nonfunctional protein precursors were identified. The plant proteases responsible for shaping the pool of endogenous peptides were predicted. Salicylic acid (SA) influenced peptide production in the secretome. The proteasome activity was altered upon SA treatment, thereby influencing the composition of the peptide pools. These results shed more light on the role of proteases and posttranslational modification in the "active management" of the extracellular peptide pool in response to stress conditions. It also identifies a list of potential peptide hormones in the moss secretome for further analysis. KEYWORDS LC-MS/MS, peptidome, Physcomitrella patens, proteases, secretome 1 | INTRODUCTION Biologically active peptides play crucial roles in plant growth and development, including response to biotic and abiotic stress conditions. 1,2 However, the number of peptides in intracellular or extracellular peptidomes as well as their diversity have been underestimated for a long time. The majority of well-studied plant bioactive peptides are generated by processing inactive protein precursors and undergo posttranslational modifications (PTMs) that are essential for their biological activities. 3 Secreted peptide hormones from the cell into the extracellular space include CLAVATA3 (CLV3)/EMBRYO SURROUNDING REGION (CLE) and the C-TERMINALLY ENCODED PEPTIDE (CEP) and cysteine-rich peptides, such as RAPID ALKALINIZATION FACTOR (RALF), which control growth and development processes, cell proliferation, and differentiation. 4,5 The release of peptides from inactive preproteins depends on the activity of specific proteases. 6 According to the structural features of their active centers, plant proteases can be divided into the following classes: serine-, cysteine-, metallo-, threonine-and aspartic-type proteases. 7 For example, the formation of AtRALF1 and AtRALF23 peptides depends on precursor cleavageby subtilisin-like proteinase S1P/SBT6.1 (serine-type), 8-10 and phytaspases (aspartic-type) were shown to cleave prosystemin in tomato. 11 In addition, proteasomes, which have caspase-like, trypsinlike, and chymotrypsin-like activities, 12-17 can be responsible for the generation of peptide pools in animal cells. 18,19 However, it is not known whether proteasomes influence peptide pools in plant cells and secretomes. Plant cells contain a mixture of 26S and 20S proteasomes that perform ubiquitin-dependent and ubiquitinindependent proteolysis. It has been shown that increased activity of the 20S pro...

show abstract

Analysis of the Yeast Peptidome and Comparison with the Human Peptidome

Cited by 35 publications

References 63 publications

Peptides from Natural or Rationally Designed Sources Can Be Used in Overweight, Obesity, and Type 2 Diabetes Therapies

Peptides from Natural or Rationally Designed Sources Can Be Used in Overweight, Obesity, and Type 2 Diabetes Therapies

The Relevance of Thimet Oligopeptidase in the Regulation of Energy Metabolism and Diet-Induced Obesity

Salicylic acid influences the protease activity and posttranslation modifications of the secreted peptides in the moss Physcomitrella patens

Contact Info

Product

Resources

About