Search results for "Transducin"
showing 10 items of 169 documents
Intracellular osteopontin protects from autoimmunity-driven lymphoma development inhibiting TLR9-MYD88-STAT3 signaling
2022
Abstract Background Autoimmune disorders, including Systemic Lupus Erythematosus (SLE), are associated with increased incidence of hematological malignancies. The matricellular protein osteopontin (OPN) has been linked to SLE pathogenesis, as SLE patients show increased serum levels of OPN and often polymorphisms in its gene. Although widely studied for its pro-tumorigenic role in different solid tumours, the role of OPN in autoimmunity-driven lymphomagenesis has not been investigated yet. Methods To test the role of OPN in the SLE-associated lymphomagenesis, the SLE-like prone Faslpr/lpr mutation was transferred onto an OPN-deficient background. Spleen from Faslpr/lpr and OPN-/-Faslpr/lpr …
PARD3 Inactivation in Lung Squamous Cell Carcinomas Impairs STAT3 and Promotes Malignant Invasion.
2015
Abstract Correct apicobasal polarization and intercellular adhesions are essential for the appropriate development of normal epithelia. Here, we investigated the contribution of the cell polarity regulator PARD3 to the development of lung squamous cell carcinomas (LSCC). Tumor-specific PARD3 alterations were found in 8% of LSCCs examined, placing PARD3 among the most common tumor suppressor genes in this malignancy. Most PAR3-mutant proteins exhibited a relative reduction in the ability to mediate formation of tight junctions and actin-based protrusions, bind atypical protein kinase C, activate RAC1, and activate STAT3 at cell confluence. Thus, PARD3 alterations prevented the formation of c…
Physical and Genetic Interactions Link the Yeast Protein Zds1p with mRNA Nuclear Export
2005
Eukaryotic gene expression requires the export of mRNA from the nucleus to the cytoplasm. The DEAD box protein Dbp5p is an essential export factor conserved from yeast to man. A fraction of Dbp5p forms a complex with nucleoporins of the cytoplasmic filaments of the nuclear pore complex. Gfd1p was identified originally as a multicopy suppressor of the rat8-2 ts allele of DBP5. Here we reported that Dbp5p and Gfd1p interact with Zds1p, a protein previously identified as a multicopy suppressor in several yeast genetic screens. By using the two-hybrid system, we showed that Zds1p interacts in vivo with both Gfd1p and Dbp5p. In vitro binding experiments revealed that Gfd1p and Dbp5p bind directl…
Zasp/Cypher internal ZM-motif containing fragments are sufficient to co-localize with α-actinin—Analysis of patient mutations
2005
Z-band alternatively spliced PDZ-containing protein (ZASP/Cypher) has an important role in maintaining Z-disc stability in striated and cardiac muscle. ZASP/Cypher interacts through its PDZ domain with the major Z-disc actin cross-linker, alpha-actinin. ZASP/Cypher also has a conserved sequence called the ZM-motif, and it is found in two alternatively spliced exons 4 and 6. We have shown earlier that the ZM-motif containing internal regions of two related proteins ALP and CLP36 interact with alpha-actinin rod region, and that the ZM-motif is important in targeting ALP to the alpha-actinin containing structures in cell. Here, we show that the ZASP/Cypher internal fragments containing either …
A novel Usher protein network at the periciliary reloading point between molecular transport machineries in vertebrate photoreceptor cells.
2008
Contains fulltext : 69178.pdf (Publisher’s version ) (Closed access) The human Usher syndrome (USH) is the most frequent cause of combined deaf-blindness. USH is genetically heterogeneous with at least 12 chromosomal loci assigned to three clinical types, USH1-3. Although these USH types exhibit similar phenotypes in human, the corresponding gene products belong to very different protein classes and families. The scaffold protein harmonin (USH1C) was shown to integrate all identified USH1 and USH2 molecules into protein networks. Here, we analyzed a protein network organized in the absence of harmonin by the scaffold proteins SANS (USH1G) and whirlin (USH2D). Immunoelectron microscopic anal…
Phosphorylation of the Usher syndrome 1G protein SANS controls Magi2-mediated endocytosis.
2014
Item does not contain fulltext The human Usher syndrome (USH) is a complex ciliopathy with at least 12 chromosomal loci assigned to three clinical subtypes, USH1-3. The heterogeneous USH proteins are organized into protein networks. Here, we identified Magi2 (membrane-associated guanylate kinase inverted-2) as a new component of the USH protein interactome, binding to the multifunctional scaffold protein SANS (USH1G). We showed that the SANS-Magi2 complex assembly is regulated by the phosphorylation of an internal PDZ-binding motif in the sterile alpha motif domain of SANS by the protein kinase CK2. We affirmed Magi2's role in receptor-mediated, clathrin-dependent endocytosis and showed tha…
Molecular basis of human Usher syndrome: deciphering the meshes of the Usher protein network provides insights into the pathomechanisms of the Usher …
2006
Usher syndrome (USH) is the most frequent cause of combined deaf-blindness in man. It is clinically and genetically heterogeneous and at least 12 chromosomal loci are assigned to three clinical USH types, namely USH1A-G, USH2A-C, USH3A (Davenport, S.L.H., Omenn, G.S., 1977. The heterogeneity of Usher syndrome. Vth Int. Conf. Birth Defects, Montreal; Petit, C., 2001. Usher syndrome: from genetics to pathogenesis. Annu. Rev. Genomics Hum. Genet. 2, 271-297). Mutations in USH type 1 genes cause the most severe form of USH. In USH1 patients, congenital deafness is combined with a pre-pubertal onset of retinitis pigmentosa (RP) and severe vestibular dysfunctions. Those with USH2 have moderate to…
The GRIP1/14-3-3 Pathway Coordinates Cargo Trafficking and Dendrite Development
2014
SummaryRegulation of cargo transport via adaptor molecules is essential for neuronal development. However, the role of PDZ scaffolding proteins as adaptors in neuronal cargo trafficking is still poorly understood. Here, we show by genetic deletion in mice that the multi-PDZ domain scaffolding protein glutamate receptor interacting protein 1 (GRIP1) is required for dendrite development. We identify an interaction between GRIP1 and 14-3-3 proteins that is essential for the function of GRIP1 as an adaptor protein in dendritic cargo transport. Mechanistically, 14-3-3 binds to the kinesin-1 binding region in GRIP1 in a phospho-dependent manner and detaches GRIP1 from the kinesin-1 motor protein …
Direct interaction of the Usher syndrome 1G protein SANS and myomegalin in the retina
2011
Contains fulltext : 96822.pdf (Publisher’s version ) (Closed access) The human Usher syndrome (USH) is the most frequent cause of combined hereditary deaf-blindness. USH is genetically heterogeneous with at least 11 chromosomal loci assigned to 3 clinical types, USH1-3. We have previously demonstrated that all USH1 and 2 proteins in the eye and the inner ear are organized into protein networks by scaffold proteins. This has contributed essentially to our current understanding of the function of USH proteins and explains why defects in proteins of different families cause very similar phenotypes. We have previously shown that the USH1G protein SANS (scaffold protein containing ankyrin repeat…
Proteomic analysis reveals a role for Bcl2-associated athanogene 3 and major vault protein in resistance to apoptosis in senescent cells by regulatin…
2014
Senescence is a prominent solid tumor response to therapy in which cells avoid apoptosis and instead enter into prolonged cell cycle arrest. We applied a quantitative proteomics screen to identify signals that lead to therapy-induced senescence and discovered that Bcl2-associated athanogene 3 (Bag3) is up-regulated after adriamycin treatment in MCF7 cells. Bag3 is a member of the BAG family of co-chaperones that interacts with Hsp70. Bag3 also regulates major cell-signaling pathways. Mass spectrometry analysis of the Bag3 Complex revealed a novel interaction between Bag3 and Major Vault Protein (MVP). Silencing of Bag3 or MVP shifts the cellular response to adriamycin to favor apoptosis. We…