Regulation of TGF- Family Activity by Proprotein Processing

2006 ◽  
pp. 53-76
Keyword(s):  
Proprotein Processing ◽  
Family Activity

Structure and mechanism of the γ-glutamyl-γ-aminobutyrate hydrolase SpuA from Pseudomonas aeruginosa

2021 ◽  
Vol 77 (10) ◽  
pp. 1305-1316
Author(s):  
Yujing Chen ◽  
Haizhu Jia ◽  
Jianyu Zhang ◽  
Yakun Liang ◽  
Ruihua Liu ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Catalytic Mechanism ◽  
Substrate Binding ◽  
Binding Pocket ◽  
Class I ◽  
Polyamine Metabolism ◽  
Binding Assays ◽  
Starting Point ◽  
Family Activity ◽  
Living Organisms

Polyamines are important regulators in all living organisms and are implicated in essential biological processes including cell growth, differentiation and apoptosis. Pseudomonas aeruginosa possesses an spuABCDEFGHI gene cluster that is involved in the metabolism and uptake of two polyamines: spermidine and putrescine. In the proposed γ-glutamylation–putrescine metabolism pathway, SpuA hydrolyzes γ-glutamyl-γ-aminobutyrate (γ-Glu-GABA) to glutamate and γ-aminobutyric acid (GABA). In this study, crystal structures of P. aeruginosa SpuA are reported, confirming it to be a member of the class I glutamine amidotransferase (GAT) family. Activity and substrate-binding assays confirm that SpuA exhibits a preference for γ-Glu-GABA as a substrate. Structures of an inactive H221N mutant were determined with bound glutamate thioester intermediate or glutamate product, thus delineating the active site and substrate-binding pocket and elucidating the catalytic mechanism. The crystal structure of another bacterial member of the class I GAT family from Mycolicibacterium smegmatis (MsGATase) in complex with glutamine was determined for comparison and reveals a binding site for glutamine. Activity assays confirm that MsGATase has activity for glutamine as a substrate but not for γ-Glu-GABA. The work reported here provides a starting point for further investigation of polyamine metabolism in P. aeruginosa.

scholarly journals Developmental expression of proprotein-processing endoprotease furin in rat pancreatic islets.

Endocrinology ◽  
1996 ◽  
Vol 137 (11) ◽  
pp. 5126-5134 ◽  
Author(s):  
T Kayo ◽  
Y Konda ◽  
S Tanaka ◽  
K Takata ◽  
A Koizumi ◽  
...  
Keyword(s):  
Pancreatic Islets ◽  
Developmental Expression ◽  
Rat Pancreatic Islets ◽  
Proprotein Processing

scholarly journals HIV-1 proprotein processing as a target for gene therapy

Gene Therapy ◽  
2003 ◽  
Vol 10 (6) ◽  
pp. 467-477 ◽  
Author(s):  
P Cordelier ◽  
M A Zern ◽  
D S Strayer
Keyword(s):  
Gene Therapy ◽  
Proprotein Processing ◽  
Hiv 1

The Influence of Attending Festivals with Children on Family Quality of Life, Subjective Well-Being, and Event Experience

2021 ◽  
Author(s):  
Yi Liu ◽  
Jason Draper
Keyword(s):  
Quality Of Life ◽  
Family Relationships ◽  
Structural Equation ◽  
Well Being ◽  
Equation Modeling ◽  
Family Quality Of Life ◽  
Subjective Well Being ◽  
Family Activity ◽  
The Relationship

Participants attending a festival(s) with children is a family activity that influences family relationships. This study examines the relationship between attending status (e.g., with or without children), event experience, subjective well-being, and family quality of life (FQOL). A total of 585 festival participants’ data analyzed by structural equation modeling (SEM) revealed that participants attending with children have a higher level of subjective well-being and FQOL compared to those without children. Participants attending with children have a higher level of cognitive engagement and experience novelty in festivals compared to those without children. Event experience results in a significant positive relationship with subjective well-being. This study expands current event literature in terms of FQOL and provides a practical guideline to event organizers to better understand the significance of festivals.

scholarly journals Targeting melanoma’s MCL1 bias unleashes the apoptotic potential of BRAF and ERK1/2 pathway inhibitors

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Matthew J. Sale ◽  
Emma Minihane ◽  
Noel R. Monks ◽  
Rebecca Gilley ◽  
Frances M. Richards ◽  
...  
Keyword(s):  
Cell Death ◽  
Patient Outcomes ◽  
Tumour Growth ◽  
Therapeutic Index ◽  
Synthetic Lethal ◽  
Bcl2 Family ◽  
Family Activity ◽  
Pathway Inhibition ◽  
Tumour Cell Death

AbstractBRAF and MEK1/2 inhibitors are effective in melanoma but resistance inevitably develops. Despite increasing the abundance of pro-apoptotic BIM and BMF, ERK1/2 pathway inhibition is predominantly cytostatic, reflecting residual pro-survival BCL2 family activity. Here, we show that uniquely low BCL-XL expression in melanoma biases the pro-survival pool towards MCL1. Consequently, BRAF or MEK1/2 inhibitors are synthetic lethal with the MCL1 inhibitor AZD5991, driving profound tumour cell death that requires BAK/BAX, BIM and BMF, and inhibiting tumour growth in vivo. Combination of ERK1/2 pathway inhibitors with BCL2/BCL-w/BCL-XL inhibitors is stronger in CRC, correlating with a low MCL1:BCL-XL ratio; indeed the MCL1:BCL-XL ratio is predictive of ERK1/2 pathway inhibitor synergy with MCL1 or BCL2/BCL-w/BCL-XL inhibitors. Finally, AZD5991 delays acquired BRAFi/MEKi resistance and enhances the efficacy of an ERK1/2 inhibitor in a model of acquired BRAFi + MEKi resistance. Thus combining ERK1/2 pathway inhibitors with MCL1 antagonists in melanoma could improve therapeutic index and patient outcomes.

Peptides as tools for studying propeptide and proprotein processing

1997 ◽  
Vol 352 (1-3) ◽  
pp. 155-178 ◽  
Author(s):  
Mohamed Rholam ◽  
Paul Cohen
Keyword(s):  
Proprotein Processing
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