scholarly journals The Catalytic and Protein-Protein Interaction Domains Are Required for APM1 Function

2010 ◽  
Vol 152 (4) ◽  
pp. 2158-2172 ◽  
Author(s):  
Fazeeda N. Hosein ◽  
Anindita Bandyopadhyay ◽  
Wendy Ann Peer ◽  
Angus S. Murphy
Keyword(s):  
Protein Interaction ◽  
Protein Protein Interaction ◽  
Interaction Domains

scholarly journals Mutations and Protein Interaction Landscape Reveal Key Cellular Events Perturbed in Upper Motor Neurons with HSP and PLS

2021 ◽  
Vol 11 (5) ◽  
pp. 578
Author(s):  
Oge Gozutok ◽  
Benjamin Ryan Helmold ◽  
P. Hande Ozdinler
Keyword(s):  
Motor Neurons ◽  
Protein Interaction ◽  
Protein Interactions ◽  
Cortical Neurons ◽  
Therapeutic Interventions ◽  
Functional Identification ◽  
Protein Protein Interaction ◽  
Cellular Events ◽  
Interaction Domains ◽  
Upper Motor Neurons

Hereditary spastic paraplegia (HSP) and primary lateral sclerosis (PLS) are rare motor neuron diseases, which affect mostly the upper motor neurons (UMNs) in patients. The UMNs display early vulnerability and progressive degeneration, while other cortical neurons mostly remain functional. Identification of numerous mutations either directly linked or associated with HSP and PLS begins to reveal the genetic component of UMN diseases. Since each of these mutations are identified on genes that code for a protein, and because cellular functions mostly depend on protein-protein interactions, we hypothesized that the mutations detected in patients and the alterations in protein interaction domains would hold the key to unravel the underlying causes of their vulnerability. In an effort to bring a mechanistic insight, we utilized computational analyses to identify interaction partners of proteins and developed the protein-protein interaction landscape with respect to HSP and PLS. Protein-protein interaction domains, upstream regulators and canonical pathways begin to highlight key cellular events. Here we report that proteins involved in maintaining lipid homeostasis and cytoarchitectural dynamics and their interactions are of great importance for UMN health and stability. Their perturbation may result in neuronal vulnerability, and thus maintaining their balance could offer therapeutic interventions.

scholarly journals Impacts of protein-protein interaction domains on organism and network complexity

2008 ◽  
Vol 18 (9) ◽  
pp. 1500-1508 ◽  
Author(s):  
K. Xia ◽  
Z. Fu ◽  
L. Hou ◽  
J.-D. J. Han
Keyword(s):  
Protein Interaction ◽  
Protein Protein Interaction ◽  
Interaction Domains

Recognition of Proline-Rich Motifs by Protein-Protein-Interaction Domains

2005 ◽  
Vol 44 (19) ◽  
pp. 2852-2869 ◽  
Author(s):  
Linda J. Ball ◽  
Ronald Kühne ◽  
Jens Schneider-Mergener ◽  
Hartmut Oschkinat
Keyword(s):  
Protein Interaction ◽  
Protein Protein Interaction ◽  
Interaction Domains

scholarly journals LRRK2 GTPase dysfunction in the pathogenesis of Parkinson's disease

2012 ◽  
Vol 40 (5) ◽  
pp. 1074-1079 ◽  
Author(s):  
Yulan Xiong ◽  
Valina L. Dawson ◽  
Ted M. Dawson
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Protein Interaction ◽  
Kinase Activity ◽  
Present Review ◽  
Signalling Pathways ◽  
Gtpase Activity ◽  
Leucine Rich Repeat ◽  
Protein Protein Interaction ◽  
Interaction Domains

Mutations in the LRRK2 (leucine-rich repeat kinase 2) gene are the most frequent genetic cause of PD (Parkinson's disease), and these mutations play important roles in sporadic PD. The LRRK2 protein contains GTPase and kinase domains and several protein–protein interaction domains. The kinase and GTPase activity of LRRK2 seem to be important in regulating LRRK2-dependent cellular signalling pathways. LRRK2's GTPase and kinase domains may reciprocally regulate each other to direct LRRK2's ultimate function. Although most LRRK2 investigations are centred on LRRK2's kinase activity, the present review focuses on the function of LRRK2's GTPase activity in LRRK2 physiology and pathophysiology.

scholarly journals Mutational Definition of RNA-binding and Protein-Protein Interaction Domains of Heterogeneous Nuclear RNP C1

2000 ◽  
Vol 276 (10) ◽  
pp. 7681-7688 ◽  
Author(s):  
Lili Wan ◽  
Jeong-Kook Kim ◽  
Victoria W. Pollard ◽  
Gideon Dreyfuss
Keyword(s):  
Protein Interaction ◽  
Rna Binding ◽  
Protein Protein Interaction ◽  
Interaction Domains ◽  
Definition Of

Crucial role of the C-terminus of PTEN in antagonizing NEDD4-1-mediated PTEN ubiquitination and degradation

2008 ◽  
Vol 414 (2) ◽  
pp. 221-229 ◽  
Author(s):  
Xinjiang Wang ◽  
Yuji Shi ◽  
Junru Wang ◽  
Guochang Huang ◽  
Xuejun Jiang
Keyword(s):  
Protein Interaction ◽  
Critical Role ◽  
Inhibitory Effect ◽  
Ww Domains ◽  
Protein Protein Interaction ◽  
Cellular Analysis ◽  
C Terminus ◽  
Tryptophan Residues ◽  
Interaction Domains ◽  
Phosphatase And Tensin Homologue

PTEN (phosphatase and tensin homologue deleted on chromosome 10), a potent tumour suppressor and multifunctional signalling protein, is under intricate regulation. In the present study, we have investigated the mechanism and regulation of PTEN ubiquitination catalysed by NEDD4-1 (neural-precursor-cell-expressed, developmentally down-regulated 4-1), a ubiquitin ligase for PTEN we identified recently. Using the reconstituted assay and cellular analysis, we demonstrated that NEDD4-1-mediated PTEN ubiquitination depends on its intact HECT (homologous to E6-associated protein C-terminus) domain. Instead of using its WW domains (protein–protein interaction domains containing two conserved tryptophan residues) as a protein interaction module, NEDD4-1 interacts with PTEN through its N-terminal region containing a C2 domain as well as the HECT domain. Strikingly, we found that a C-terminal truncated PTEN fragment binds to NEDD4-1 with higher affinity than the full-length PTEN, suggesting an intrinsic inhibitory effect of the PTEN C-terminus on PTEN–NEDD4-1 interaction. Moreover, the C-terminal truncated PTEN is more sensitive to NEDD4-1-mediated ubiquitination and degradation. Therefore the present study reveals that the C-terminus of PTEN plays a critical role in stabilizing PTEN via antagonizing NEDD4-1-induced PTEN protein decay; conversely, truncation of the PTEN C-terminus results in rapid NEDD4-1-mediated PTEN degradation, a possible mechanism accounting for attenuation of PTEN function by certain PTEN mutations in human cancers.

Recognition of Proline-Rich Motifs by Protein—Protein-Interaction Domains

ChemInform ◽  
2005 ◽  
Vol 36 (52) ◽  
Author(s):  
Linda J. Ball ◽  
Ronald Kuehne ◽  
Jens Schneider-Mergener ◽  
Hartmut Oschkinat
Keyword(s):  
Protein Interaction ◽  
Protein Protein Interaction ◽  
Interaction Domains
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