Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aip3p is an actin-interacting protein that regulates cell polarity in budding yeast. The Schizosaccharomyces pombe-sequencing project recently led to the identification of a homologue of Aip3p that we have named spAip3p. Our results confirm that spAip3p is a true functional homologue of Aip3p. When expressed in budding yeast, spAip3p localizes similarly to Aip3p during the cell cycle and complements the cell polarity defects of an aip3Delta strain. Two-hybrid analysis shows that spAip3p interacts with actin similarly to Aip3p. In fission yeast, spAip3p localizes to both cell ends during interphase and later organizes into two rings at the site of cytokinesis. spAip3p localization to cell ends is dependent on microtubule cytoskeleton, its localization to the cell middle is dependent on actin cytoskeleton, and both patterns of localization require an operative secretory pathway. Overexpression of spAip3p disrupts the actin cytoskeleton and cell polarity, leading to morphologically aberrant cells. Fission yeast, which normally rely on the microtubule cytoskeleton to establish their polarity axis, can use the actin cytoskeleton in the absence of microtubule function to establish a new polarity axis, leading to the formation of branched cells. spAip3p localizes to, and is required for, branch formation, confirming its role in actin-directed polarized cell growth in both Schizosaccharomyces pombe and Saccharomyces cerevisiae.
Mol Biol Cell 2001 May
PMID:Fission yeast Aip3p (spAip3p) is required for an alternative actin-directed polarity program. 1135 21

The mSin3A-histone deacetylase corepressor is a multiprotein complex that is recruited by DNA binding transcriptional repressors. Sin3 has four paired amphipathic alpha helices (PAH1 to -4) that are protein-protein interaction motifs and is the scaffold upon which the complex assembles. We identified a novel mSin3A-interacting protein that has two plant homeodomain (PHD) zinc fingers we term Pf1, for PHD factor one. Pf1 associates with mSin3A in vivo and recruits the mSin3A complex to repress transcription when fused to the DNA binding domain of Gal4. Pf1 interacts with Sin3 through two independent Sin3 interaction domains (SIDs), Pf1SID1 and Pf1SID2. Pf1SID1 binds PAH2, while Pf1SID2 binds PAH1. Pf1SID1 has sequence and structural similarity to the well-characterized 13-amino-acid SID of the Mad bHLHZip repressor. Pf1SID2 does not have sequence similarity with either Mad SID or Pf1SID1 and therefore represents a novel Sin3 binding domain. Mutations in a minimal fragment of Pf1 that encompasses Pf1SID1 inhibited mSin3A binding yet only slightly impaired repression when targeted to DNA, implying that Pf1 might interact with other corepressors. We show that Pf1 interacts with a mammalian homolog of the Drosophila Groucho corepressor, transducin-like enhancer (TLE). Pf1 binds TLE in an mSin3A-independent manner and recruits functional TLE complexes to repress transcription. These findings suggest that Pf1 may serve to bridge two global transcription networks, mSin3A and TLE.
Mol Cell Biol 2001 Jul
PMID:Pf1, a novel PHD zinc finger protein that links the TLE corepressor to the mSin3A-histone deacetylase complex. 1139 Jun 40

Myosin Va is associated with discrete vesicle populations in a number of cell types, but little is known of the function of myosin Vb. Yeast two-hybrid screening of a rabbit parietal cell cDNA library with dominant active Rab11a (Rab11aS20V) identified myosin Vb as an interacting protein for Rab11a, a marker for plasma membrane recycling systems. The isolated clone, corresponding to the carboxyl terminal 60 kDa of the myosin Vb tail, interacted with all members of the Rab11 family (Rab11a, Rab11b, and Rab25). GFP-myosin Vb and endogenous myosin Vb immunoreactivity codistributed with Rab11a in HeLa and Madin-Darby canine kidney (MDCK) cells. As with Rab11a in MDCK cells, the myosin Vb immunoreactivity was dispersed with nocodazole treatment and relocated to the apical corners of cells with taxol treatment. A green fluorescent protein (GFP)-myosin Vb tail chimera overexpressed in HeLa cells retarded transferrin recycling and caused accumulation of transferrin and the transferrin receptor in pericentrosomal vesicles. Expression of the myosin Vb tail chimera in polarized MDCK cells stably expressing the polymeric IgA receptor caused accumulation of basolaterally endocytosed polymeric IgA and the polymeric IgA receptor in the pericentrosomal region. The myosin Vb tail had no effects on transferrin trafficking in polarized MDCK cells. The GFP-myosin Va tail did not colocalize with Rab11a and had no effects on recycling system vesicle distribution in either HeLa or MDCK cells. The results indicate myosin Vb is associated with the plasma membrane recycling system in nonpolarized cells and the apical recycling system in polarized cells. The dominant negative effects of the myosin Vb tail chimera indicate that this unconventional myosin is required for transit out of plasma membrane recycling systems.
Mol Biol Cell 2001 Jun
PMID:Myosin vb is associated with plasma membrane recycling systems. 1140 90

CDC25A phosphatase promotes cell cycle progression by activating G(1) cyclin-dependent kinases and has been postulated to be an oncogene because of its ability to cooperate with RAS to transform rodent fibroblasts. In this study, we have identified apoptosis signal-regulating kinase 1 (ASK1) as a CDC25A-interacting protein by yeast two-hybrid screening. ASK1 activates the p38 mitogen-activated protein kinase (MAPK) and c-Jun NH(2)-terminal protein kinase-stress-activated protein kinase (JNK/SAPK) pathways upon various cellular stresses. Coimmunoprecipitation studies demonstrated that CDC25A physically associates with ASK1 in mammalian cells, and immunocytochemistry with confocal laser-scanning microscopy showed that these two proteins colocalize in the cytoplasm. The carboxyl terminus of CDC25A binds to a domain of ASK1 adjacent to its kinase domain and inhibits the kinase activity of ASK1, independent of and without effect on the phosphatase activity of CDC25A. This inhibitory action of CDC25A on ASK1 activity involves diminished homo-oligomerization of ASK1. Increased cellular expression of wild-type or phosphatase-inactive CDC25A from inducible transgenes suppresses oxidant-dependent activation of ASK1, p38, and JNK1 and reduces specific sensitivity to cell death triggered by oxidative stress, but not other apoptotic stimuli. Thus, increased expression of CDC25A, frequently observed in human cancers, could contribute to reduced cellular responsiveness to oxidative stress under mitogenic or oncogenic conditions, while it promotes cell cycle progression. These observations propose a mechanism of oncogenic transformation by the dual function of CDC25A on cell cycle progression and stress responses.
Mol Cell Biol 2001 Jul
PMID:The cell cycle-regulatory CDC25A phosphatase inhibits apoptosis signal-regulating kinase 1. 1141 55

Neurodegeneration in Huntington's disease (HD) is associated with an elongated glutamine tract in the widely expressed huntingtin protein. Although the pathogenic mechanisms are still unknown, the distinct physical properties of mutant huntingtin in the brain suggest that other factors including huntingtin-interacting proteins might play a specific role. We have previously identified a DNA-binding motif in the proximal E1A promoter of adenovirus serotype 12 as responsible for E1A autoregulation. Here, we identified the p231HBP protein as a DNA-binding factor, the C-terminal portion of which has recently been characterized as the huntingtin-interacting protein HYPB of unknown function. We have determined the full-length cDNA sequence, identified several domains supporting its gene regulatory functions, and mapped the HBP231 gene to chromosome 3p21.2-p21.3. Our results provide an interesting molecular link between huntingtin and a DNA-binding factor, implicating that this interaction might result in the alteration of cellular gene expression involved in HD pathogenesis.
Mol Cell Neurosci 2001 Jul
PMID:Identification of the full-length huntingtin- interacting protein p231HBP/HYPB as a DNA-binding factor. 1146 Nov 54

The CDK-interacting protein phosphatase KAP dephosphorylates phosphoThr-160 (pThr-160) of the CDK2 activation segment, the site of regulatory phosphorylation that is essential for kinase activity. Here we describe the crystal structure of KAP in association with pThr-160-CDK2, representing an example of a protein phosphatase in complex with its intact protein substrate. The major protein interface between the two molecules is formed by the C-terminal lobe of CDK2 and the C-terminal helix of KAP, regions remote from the kinase-activation segment and the KAP catalytic site. The kinase-activation segment interacts with the catalytic site of KAP almost entirely via the phosphate group of pThr-160. This interaction requires that the activation segment is unfolded and drawn away from the kinase molecule, inducing a conformation of CDK2 similar to the activated state observed in the CDK2/cyclin A complex.
Mol Cell 2001 Mar
PMID:Phosphoprotein-protein interactions revealed by the crystal structure of kinase-associated phosphatase in complex with phosphoCDK2. 1146 86

The common plant regulatory factors (CPRFs) from parsley are transcription factors with a basic-leucine-zipper motif that bind to cis-regulatory elements frequently found in promoters of light-regulated genes. Proposed to function in concert with members of other transcription factor families, CPRFs regulate the transcriptional activity of many target genes. Here, we report that, in contrast to CPRF2, which operates as a transcriptional activator, CPRF1 functions as repressor in vivo. Two-hybrid screens using CPRF1 and CPRF2 as "baits" resulted in the isolation of four novel parsley proteins which interact with either CPRF1 or CPRF2 in vivo. Three of these factors represent new parsley bZIP factors, designated CPRF5-CPRF7, whereas the fourth, named CPRF1-interacting protein (CIP), shows no homology to any other known protein. CPRF5 and CIP specifically interact with CPRF1, whilst CPRF6 and CPRF7 exclusively form heterodimers with CPRF2. CPRF5, CPRF6 and CPRF7 are transcription factors that exhibit sequence-specific DNA-binding as well as transactivation abilities, whereas the function of CIP remains elusive. The newly isolated CPRFs and CIP are constitutively localized in the nucleus in parsley protoplasts. Furthermore, mRNA accumulation studies revealed that the expression of these novel bZIP genes and CIP is not altered by exposure to light. We discuss the possible roles of the newly identified proteins in CPRF1- and CPRF2-dependent target gene expression.
Mol Genet Genomics 2001 Aug
PMID:Isolation and characterization of four novel parsley proteins that interact with the transcriptional regulators CPRF1 and CPRF2. 1152 88

Dysferlin is a surface membrane protein in skeletal muscle whose deficiency causes distal and proximal, recessively inherited, forms of muscular dystrophy designated Miyoshi myopathy (MM) and limb girdle muscular dystrophy type 2B (LGMD2B), respectively. The function of dysferlin is not defined. Caveolin-3 is another skeletal muscle membrane protein which is important in the formation of caveolae and whose mutations cause dominantly inherited limb girdle muscular dystrophy type 1C (LGMD1C). We report that dysferlin co-immunoprecipitates with caveolin-3 from biopsied normal human skeletal muscles. We also describe abnormal localization of dysferlin in muscles from patients with LGMD1C including novel missense mutation (T64P) in the human caveolin-3 gene (CAV3). The immunoprecipitation data are consistent with the parallel observation that dysferlin immunostaining is not normal in LGMD1C muscles. Amino acid sequence analysis of the dysferlin protein reveals seven sites that correspond to caveolin-3 scaffold-binding motifs, and one site that is a potential target to bind the WW domain of the caveolin-3 protein. This is the first description of a possible dysferlin interacting protein; it suggests the hypothesis that one function of dysferlin may be to interact with caveolin-3 to subserve signaling functions of caveolae.
Hum Mol Genet 2001 Aug 15
PMID:The sarcolemmal proteins dysferlin and caveolin-3 interact in skeletal muscle. 1153 85

Viral movement through plasmodesmata in host plants likely depends on the interaction between virus-encoded movement protein (MP) and host proteins. In order to search for MP-interacting protein (MIP), we carried out far-western screening of a Brassica campestris cDNA library using a recombinant MP of tomato mosaic tobamovirus (ToMV) as a probe. One of the positive clones, designated MIP102, was found to be a putative orthologue for a transcriptional coactivator KELP of Arabidopsis thaliana. In vitro analysis with recombinant proteins revealed that ToMV MP could bind to KELP proteins that are derived from different plant species. At least 31 amino acids from the carboxyl-terminus of ToMV MP were dispensable for the interaction with KELP. Other MPs, derived from crucifer tobamovirus CTMV-W and cucumber mosaic cucumovirus, also exhibited comparable binding abilities. This suggests that these MPs could commonly interact with KELP, possibly to modulate the host gene expression.
Mol Cells 2001 Aug 31
PMID:The tomato mosaic tobamovirus movement protein interacts with a putative transcriptional coactivator KELP. 1156 31

Prominent in T cells and natural killer cells, CD2 binding protein 1 (CD2BP1) plays an important role in CD2-mediated adhesion and signal transduction. In the current study, we investigated CD2 and PSTPIP (proline, serine, threonine phosphatase interacting protein, murine homologue of CD2BP1) interactions in purified mouse splenic T cells. PSTPIP associated with CD2 in both resting and activated T cells. Following various stimuli, such as concanavalin A, anti-TCRbeta, anti-CD3epsilon, anti-CD3epsilon/phorbol myristate acetate (PMA), IL-2, or PMA/ionomycin, PSTPIP and CD2 expression, as well as their association, increased in a time-dependent fashion. While PSTPIP expression and CD2 expression were comparable across most groups, the PSTPIP-CD2 association stimulated by anti-CD3epsilon alone was significantly greater than with other stimuli. Stimulation by anti-CD3epsilon plus anti-CD28 induced even greater PSTPIP-CD2 association than anti-CD3epsilon treatment alone, indicating that CD28 initiated signals are involved in regulating this interaction. There was no direct association between CD3epsilon or CD28 and PSTPIP. Tyrosine phosphorylated PSTPIP bound poorly to CD2 compared to dephosphorylated PSTPIP, and protein tyrosine phosphatase was shown to affect both phosphorylation of PSTPIP and the CD2-PSTPIP association. In addition to CD2, PSTPIP associated with CD4, CD8, CD54, and CD62L. CD2 and CD4 ligation reciprocally regulated their association with PSTPIP. These findings indicate that T cell activation, particularly through the CD3 and CD28 signal transduction pathways, regulates PSTPIP-CD2 interactions. PSTPIP likely has additional broader effects through interactions with CD4, CD8, CD54, and CD62L, and this may influence T cell responses to antigen.
Exp Mol Pathol 2001 Oct
PMID:Regulation of the association between PSTPIP and CD2 in murine T cells. 1159 17


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