Structure of the Amino-Terminal Protein Interaction Domain of STAT-4

Science ◽  
1998 ◽  
Vol 279 (5353) ◽  
pp. 1048-1052 ◽  
Author(s):  
U. Vinkemeier
Keyword(s):  
Protein Interaction ◽  
Terminal Protein ◽  
Interaction Domain ◽  
Amino Terminal

scholarly journals Evaluating Effects of HypomorphicThoc1Alleles on Embryonic Development inRb1Null Mice

2016 ◽  
Vol 36 (11) ◽  
pp. 1621-1627 ◽  
Author(s):  
Meenalakshmi Chinnam ◽  
Xiaoling Wang ◽  
Xiaojing Zhang ◽  
David W. Goodrich
Keyword(s):  
Embryonic Development ◽  
Protein Interaction ◽  
Tissue Expression ◽  
Regulatory Genes ◽  
Terminal Protein ◽  
Interaction Domain ◽  
Ribonucleoprotein Complex ◽  
Protein Levels ◽  
Amino Terminal ◽  
Expression Of Genes

The Rb1 tumor suppressor protein is a molecular adaptor that physically links transcription factors like E2f with various proteins acting on DNA or RNA to repress gene expression. Loss of Rb1 liberates E2f to activate the expression of genes mediating resulting phenotypes. Most Rb1 binding proteins, including E2f, interact through carboxyl-terminal protein interaction domains, but genetic evidence suggests that an amino-terminal protein interaction domain is also important. One protein that binds Rb1 through the amino-terminal domain is encoded byThoc1, a required component of the THO ribonucleoprotein complex important for RNA processing and transport. The physiological relevance of this interaction is unknown. Here we tested whetherThoc1mediates effects ofRb1loss on mouse embryonic development. We found thatThoc1deficiency delays embryo death, and this delay correlates with reduced apoptosis in the brain. E2f protein levels are reduced inRb1:Thoc1-deficient brain tissue. Expression of apoptotic regulatory genes regulated by E2f, like Apaf1 and Bak1, is also reduced. These observations suggest thatThoc1is required to support increased expression of E2f and apoptotic regulatory genes that trigger apoptosis uponRb1loss. These findings implicate Rb1 in the regulation of the THO ribonucleoprotein complex.

scholarly journals Distinct Functions of POT1 at Telomeres

2008 ◽  
Vol 28 (17) ◽  
pp. 5251-5264 ◽  
Author(s):  
Katharine S. Barrientos ◽  
Megan F. Kendellen ◽  
Brian D. Freibaum ◽  
Blaine N. Armbruster ◽  
Katherine T. Etheridge ◽  
...  
Keyword(s):  
Dna Damage ◽  
Protein Interaction ◽  
Dna Binding Protein ◽  
Binding Activity ◽  
Terminal Protein ◽  
Interaction Domain ◽  
Ssdna Binding ◽  
Double Stranded Dna ◽  
Mammalian Protein

ABSTRACT The mammalian protein POT1 binds to telomeric single-stranded DNA (ssDNA), protecting chromosome ends from being detected as sites of DNA damage. POT1 is composed of an N-terminal ssDNA-binding domain and a C-terminal protein interaction domain. With regard to the latter, POT1 heterodimerizes with the protein TPP1 to foster binding to telomeric ssDNA in vitro and binds the telomeric double-stranded-DNA-binding protein TRF2. We sought to determine which of these functions—ssDNA, TPP1, or TRF2 binding—was required to protect chromosome ends from being detected as DNA damage. Using separation-of-function POT1 mutants deficient in one of these three activities, we found that binding to TRF2 is dispensable for protecting telomeres but fosters robust loading of POT1 onto telomeric chromatin. Furthermore, we found that the telomeric ssDNA-binding activity and binding to TPP1 are required in cis for POT1 to protect telomeres. Mechanistically, binding of POT1 to telomeric ssDNA and association with TPP1 inhibit the localization of RPA, which can function as a DNA damage sensor, to telomeres.

scholarly journals Regulation of clathrin coat assembly by Eps15 homology domain–mediated interactions during endocytosis

2012 ◽  
Vol 23 (4) ◽  
pp. 687-700 ◽  
Author(s):  
Ryohei Suzuki ◽  
Junko Y. Toshima ◽  
Jiro Toshima
Keyword(s):  
Functional Diversity ◽  
Protein Interaction ◽  
Interaction Domain ◽  
Protein Protein Interaction ◽  
Molecular Events ◽  
Biological Studies ◽  
Eh Domain ◽  
Actin Patch ◽  
Lines Of Evidence

Clathrin-mediated endocytosis involves a coordinated series of molecular events regulated by interactions among a variety of proteins and lipids through specific domains. One such domain is the Eps15 homology (EH) domain, a highly conserved protein–protein interaction domain present in a number of proteins distributed from yeast to mammals. Several lines of evidence suggest that the yeast EH domain–containing proteins Pan1p, End3p, and Ede1p play important roles during endocytosis. Although genetic and cell-biological studies of these proteins suggested a role for the EH domains in clathrin-mediated endocytosis, it was unclear how they regulate clathrin coat assembly. To explore the role of the EH domain in yeast endocytosis, we mutated those of Pan1p, End3p, or Ede1p, respectively, and examined the effects of single, double, or triple mutation on clathrin coat assembly. We found that mutations of the EH domain caused a defect of cargo internalization and a delay of clathrin coat assembly but had no effect on assembly of the actin patch. We also demonstrated functional redundancy among the EH domains of Pan1p, End3p, and Ede1p for endocytosis. Of interest, the dynamics of several endocytic proteins were differentially affected by various EH domain mutations, suggesting functional diversity of each EH domain.

scholarly journals Dimerization of the RamC Morphogenetic Protein of Streptomyces coelicolor

2004 ◽  
Vol 186 (5) ◽  
pp. 1330-1336 ◽  
Author(s):  
Michael E. Hudson ◽  
Justin R. Nodwell
Keyword(s):  
Protein Kinase ◽  
Streptomyces Coelicolor ◽  
Kinase Domain ◽  
Terminal Protein ◽  
Amino Terminal ◽  
Morphogenetic Protein ◽  
Aerial Hyphae ◽  
Multiple Copies ◽  
Defective Allele

ABSTRACT RamC is required for the formation of spore-forming cells called aerial hyphae by the bacterium Streptomyces coelicolor. This protein is membrane associated and has an amino-terminal protein kinase-like domain, but little is known about its mechanism of action. In this study we found that the presence of multiple copies of a defective allele of ramC inhibits morphogenesis in S. coelicolor, consistent with either titration of a target or formation of inactive RamC multimers. We identified a domain in RamC that is C terminal to the putative kinase domain and forms a dimer with a Kd of ∼0.1 μM. These data suggest that RamC acts as a dimer in vivo.

scholarly journals Classification of Nonenzymatic Homologues of Protein Kinases

2009 ◽  
Vol 2009 ◽  
pp. 1-17 ◽  
Author(s):  
K. Anamika ◽  
K. R. Abhinandan ◽  
K. Deshmukh ◽  
N. Srinivasan
Keyword(s):  
Protein Kinase ◽  
Protein Kinases ◽  
Protein Interaction ◽  
Transmembrane Domain ◽  
Homo Sapiens ◽  
Interaction Domain ◽  
Protein Protein Interaction ◽  
Domain 3 ◽  
Eukaryotic Organisms ◽  
And Function

Protein Kinase-Like Non-kinases (PKLNKs), which are closely related to protein kinases, lack the crucial catalytic aspartate in the catalytic loop, and hence cannot function as protein kinase, have been analysed. Using various sensitive sequence analysis methods, we have recognized 82 PKLNKs from four higher eukaryotic organisms, namely,Homo sapiens,Mus musculus,Rattus norvegicus, andDrosophila melanogaster. On the basis of their domain combination and function, PKLNKs have been classified mainly into four categories: (1) Ligand binding PKLNKs, (2) PKLNKs with extracellular protein-protein interaction domain, (3) PKLNKs involved in dimerization, and (4) PKLNKs with cytoplasmic protein-protein interaction module. While members of the first two classes of PKLNKs have transmembrane domain tethered to the PKLNK domain, members of the other two classes of PKLNKs are cytoplasmic in nature. The current classification scheme hopes to provide a convenient framework to classify the PKLNKs from other eukaryotes which would be helpful in deciphering their roles in cellular processes.

A Novel BTB/POZ Transcriptional Repressor Protein Interacts With the Fanconi Anemia Group C Protein and PLZF

Blood ◽  
1999 ◽  
Vol 94 (11) ◽  
pp. 3737-3747 ◽  
Author(s):  
Maureen E. Hoatlin ◽  
Yu Zhi ◽  
Helen Ball ◽  
Kirsten Silvey ◽  
Ari Melnick ◽  
...  
Keyword(s):  
Fanconi Anemia ◽  
Transcriptional Repression ◽  
Cancer Susceptibility ◽  
Bone Marrow Failure ◽  
Severe Disease ◽  
Transcriptional Repressor ◽  
Interaction Domain ◽  
C Protein ◽  
Amino Terminal ◽  
Anemia Group

Fanconi anemia (FA) is an autosomal recessive cancer susceptibility syndrome. The phenotype includes developmental defects, bone marrow failure, and cell cycle abnormalities. At least eight complementation groups (A-H) exist, and although three of the corresponding complementation group genes have been cloned, they lack recognizable motifs, and their functions are unknown. We have isolated a binding partner for the Fanconi anemia group C protein (FANCC) by yeast two-hybrid screening. We show that the novel gene, FAZF, encodes a 486 amino acid protein containing a conserved amino terminal BTB/POZ protein interaction domain and three C-terminal Krüppel-like zinc fingers. FAZF is homologous to the promyelocytic leukemia zinc finger (PLZF) protein, which has been shown to act as a transcriptional repressor by recruitment of nuclear corepressors (N-CoR, Sin3, and HDAC1 complex). Consistent with a role in FA, BTB/POZ-containing proteins have been implicated in oncogenesis, limb morphogenesis, hematopoiesis, and proliferation. We show that FAZF is a transcriptional repressor that is able to bind to the same DNA target sequences as PLZF. Our data suggest that the FAZF/FANCC interaction maps to a region of FANCC deleted in FA patients with a severe disease phenotype. We also show that FAZF and wild-type FANCC can colocalize in nuclear foci, whereas a patient-derived mutant FANCC that is compromised for nuclear localization cannot. These results suggest that the function of FANCC may be linked to a transcriptional repression pathway involved in chromatin remodeling.

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