GLORIA

GEOMAR Library Ocean Research Information Access

X
feed icon rss

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • Articles  (25)
  • The American Society for Biochemistry and Molecular Biology (ASBMB)  (18)
  • The American Association of Immunologists (AAI)  (7)
  • 1
    facet.materialart.
    Unknown
    Mechanistic Insight into Hec1-Nuf2 Dimerization [Protein Structure and Folding] (2013)
    The American Society for Biochemistry and Molecular Biology (ASBMB)
    Details
    Publication Date: 2013-11-30
    Description: Hec1 and Nuf2, core components of the NDC80 complex, are essential for kinetochore-microtubule attachment and chromosome segregation. It has been shown that both Hec1 and Nuf2 utilize their coiled-coil domains to form a functional dimer; however, details of the consequential significance and structural requirements to form the dimerization interface have yet to be elucidated. Here, we showed that Hec1 required three contiguous heptad repeats from Leu-324 to Leu-352, but not the entire first coiled-coil domain, to ensure overall stability of the NDC80 complex through direct interaction with Nuf2. Substituting the hydrophobic core residues, Leu-331, Val-338, and Ile-345, of Hec1 with alanine completely eliminated Nuf2 binding and blocked mitotic progression. Moreover, unlike most coiled-coil proteins, where the buried positions are composed of hydrophobic residues, Hec1 possessed an unusual distribution of glutamic acid residues, Glu-334, Glu-341, and Glu-348, buried within the interior dimerization interface, which complement with three Nuf2 lysine residues: Lys-227, Lys-234, and Lys-241. Substituting these corresponding residues with alanine diminished the binding affinity between Hec1 and Nuf2, compromised NDC80 complex formation, and adversely affected mitotic progression. Taken together, these findings demonstrated that three buried glutamic acid-lysine pairs, in concert with hydrophobic interactions of core residues, provide the major specificity and stability requirements for Hec1-Nuf2 dimerization and NDC80 complex formation.
    Print ISSN: 0021-9258
    Electronic ISSN: 1083-351X
    Topics: Biology , Chemistry and Pharmacology
    Published by The American Society for Biochemistry and Molecular Biology (ASBMB)
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 2
    facet.materialart.
    Unknown
    Cypher/ZASP Is an AKAP [Molecular Bases of Disease] (2013)
    The American Society for Biochemistry and Molecular Biology (ASBMB)
    Details
    Publication Date: 2013-10-12
    Description: PKA signaling is important for the post-translational modification of proteins, especially those in cardiomyocytes involved in cardiac excitation-contraction coupling. PKA activity is spatially and temporally regulated through compartmentalization by protein kinase A anchoring proteins. Cypher/ZASP, a member of PDZ-LIM domain protein family, is a cytoskeletal protein that forms multiprotein complexes at sarcomeric Z-lines. It has been demonstrated that Cypher/ZASP plays a pivotal structural role in the structural integrity of sarcomeres, and several of its mutations are associated with myopathies including dilated cardiomyopathy. Here we show that Cypher/ZASP, interacting specifically with the type II regulatory subunit RIIα of PKA, acted as a typical protein kinase A anchoring protein in cardiomyocytes. In addition, we show that Cypher/ZASP itself was phosphorylated at Ser265 and Ser296 by PKA. Furthermore, the PDZ domain of Cypher/ZASP interacted with the L-type calcium channel through its C-terminal PDZ binding motif. Expression of Cypher/ZASP facilitated PKA-mediated phosphorylation of the L-type calcium channel in vitro. Additionally, the phosphorylation of the L-type calcium channel at Ser1928 induced by isoproterenol was impaired in neonatal Cypher/ZASP-null cardiomyocytes. Moreover, Cypher/ZASP interacted with the Ser/Thr phosphatase calcineurin, which is a phosphatase for the L-type calcium channel. Taken together, our data strongly suggest that Cypher/ZASP not only plays a structural role for the sarcomeric integrity, but is also an important sarcomeric signaling scaffold in regulating the phosphorylation of channels or contractile proteins.
    Print ISSN: 0021-9258
    Electronic ISSN: 1083-351X
    Topics: Biology , Chemistry and Pharmacology
    Published by The American Society for Biochemistry and Molecular Biology (ASBMB)
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 3
    facet.materialart.
    Unknown
    HNF6 Inhibits EMT and Lung Cancer Cell Growth [Molecular Bases of Disease] (2013)
    The American Society for Biochemistry and Molecular Biology (ASBMB)
    Details
    Publication Date: 2013-10-26
    Description: Epithelial-mesenchymal transition plays an important role in many patho-physiological processes, including cancer invasion and metastatic progression. Hepatocyte nuclear factor 6 (HNF6) has been known to be an important factor for both physiological and pathological functions in liver and pancreas. However, its role in EMT and lung cancer progression remains unidentified. We observed that HNF6 level can be down-regulated by TGF-β1 in human lung cancer cells. Knockdown of HNF6 induced EMT and increased cell migration. In contrast, ectopically expression of HNF6 inhibited cell migration and attenuated TGF-β1-induced EMT. The data suggest that HNF6 plays a role in maintaining epithelial phenotype, which suppresses EMT. HNF6 also inhibits both colony formation and proliferation of lung cancer cells. It pronouncedly reduced the formation of tumor xenografts in nude mice. In addition, HNF6 can activate the promoter activity of p53 by directly binding to a specific region of its promoter and therefore increase the protein level of tumor suppressor p53. p53 knockdown induced EMT and increased cell migration, whereas the opposite effect was generated by p53 overexpression. p53 knockdown also inhibited the effect of HNF6 on EMT and cell migration, indicating that p53 is required for the functions of HNF6 herein. Moreover, there is a high positive correlation among the expression levels of HNF6, p53, and E-cadherin in human lung cancer cells and tissues. The data suggest that HNF6 inhibits EMT, cell migration, and invasive growth through a mechanism involving the transcriptional activation of p53.
    Print ISSN: 0021-9258
    Electronic ISSN: 1083-351X
    Topics: Biology , Chemistry and Pharmacology
    Published by The American Society for Biochemistry and Molecular Biology (ASBMB)
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 4
    facet.materialart.
    Unknown
    Protein 4.1R and Intestinal Calcium Absorption [Membrane Biology] (2013)
    The American Society for Biochemistry and Molecular Biology (ASBMB)
    Details
    Publication Date: 2013-04-20
    Description: Protein 4.1R was first identified in the erythrocyte membrane skeleton. It is now known that the protein is expressed in a variety of epithelial cell lines and in the epithelia of many tissues, including the small intestine. However, the physiological function of 4.1R in the epithelial cells of the small intestine has not so far been explored. Here, we show that 4.1R knock-out mice exhibited a significantly impaired small intestinal calcium absorption that resulted in secondary hyperparathyroidism as evidenced by increased serum 1,25-(OH)2-vitamin D3 and parathyroid hormone levels, decreased serum calcium levels, hyperplasia of the parathyroid, and demineralization of the bones. 4.1R is located on the basolateral membrane of enterocytes, where it co-localizes with PMCA1b (plasma membrane calcium ATPase 1b). Expression of PMCA1b in enterocytes was decreased in 4.1−/− mice. 4.1R directly associated with PMCA1b, and the association involved the membrane-binding domain of 4.1R and the second intracellular loop and C terminus of PMCA1b. Our findings have enabled us to define a functional role for 4.1R in small intestinal calcium absorption through regulation of membrane expression of PMCA1b.
    Print ISSN: 0021-9258
    Electronic ISSN: 1083-351X
    Topics: Biology , Chemistry and Pharmacology
    Published by The American Society for Biochemistry and Molecular Biology (ASBMB)
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 5
    facet.materialart.
    Unknown
    RAG1/2 Knockout Pigs with Severe Combined Immunodeficiency [NOVEL IMMUNOLOGICAL METHODS] (2014)
    The American Association of Immunologists (AAI)
    Details
    Publication Date: 2014-07-22
    Description: Pigs share many physiological, biochemical, and anatomical similarities with humans and have emerged as valuable large animal models for biomedical research. Considering the advantages in immune system resemblance, suitable size, and longevity for clinical practical and monitoring purpose, SCID pigs bearing dysfunctional RAG could serve as important experimental tools for regenerative medicine, allograft and xenograft transplantation, and reconstitution experiments related to the immune system. In this study, we report the generation and phenotypic characterization of RAG1 and RAG2 knockout pigs using transcription activator-like effector nucleases. Porcine fetal fibroblasts were genetically engineered using transcription activator-like effector nucleases and then used to provide donor nuclei for somatic cell nuclear transfer. We obtained 27 live cloned piglets; among these piglets, 9 were targeted with biallelic mutations in RAG1, 3 were targeted with biallelic mutations in RAG2, and 10 were targeted with a monoallelic mutation in RAG2. Piglets with biallelic mutations in either RAG1 or RAG2 exhibited hypoplasia of immune organs, failed to perform V(D)J rearrangement, and lost mature B and T cells. These immunodeficient RAG1/2 knockout pigs are promising tools for biomedical and translational research.
    Print ISSN: 0022-1767
    Electronic ISSN: 1550-6606
    Topics: Medicine
    Published by The American Association of Immunologists (AAI)
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 6
    facet.materialart.
    Unknown
    SUV3{middle dot}PNPase{middle dot}mtPAP Modulate mt-mRNA Poly(A) Tails [Enzymology] (2014)
    The American Society for Biochemistry and Molecular Biology (ASBMB)
    Details
    Publication Date: 2014-06-14
    Description: Mammalian mitochondrial mRNA (mt-mRNA) transcripts are polyadenylated at the 3′ end with different lengths. The SUV3·PNPase complex and mtPAP have been shown to degrade and polyadenylate mt mRNA, respectively. How these two opposite actions are coordinated to modulate mt-mRNA poly(A) lengths is of interest to pursue. Here, we demonstrated that a fraction of the SUV3·PNPase complex interacts with mitochondrial polyadenylation polymerase (mtPAP) under low mitochondrial matrix inorganic phosphate (Pi) conditions. In vitro binding experiments using purified proteins suggested that SUV3 binds to mtPAP through the N-terminal region around amino acids 100–104, distinctive from the C-terminal region around amino acids 510–514 of SUV3 for PNPase binding. mtPAP does not interact with PNPase directly, and SUV3 served as a bridge capable of simultaneously binding with mtPAP and PNPase. The complex consists of a SUV3 dimer, a mtPAP dimer, and a PNPase trimer, based on the molecular sizing experiments. Mechanistically, SUV3 provides a robust single strand RNA binding domain to enhance the polyadenylation activity of mtPAP. Furthermore, purified SUV3·PNPase·mtPAP complex is capable of lengthening or shortening the RNA poly(A) tail lengths in low or high Pi/ATP ratios, respectively. Consistently, the poly(A) tail lengths of mt-mRNA transcripts can be lengthened or shortened by altering the mitochondrial matrix Pi levels via selective inhibition of the electron transport chain or ATP synthase, respectively. Taken together, these results suggested that SUV3·PNPase·mtPAP form a transient complex to modulate mt-mRNA poly(A) tail lengths in response to cellular energy changes.
    Print ISSN: 0021-9258
    Electronic ISSN: 1083-351X
    Topics: Biology , Chemistry and Pharmacology
    Published by The American Society for Biochemistry and Molecular Biology (ASBMB)
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 7
    facet.materialart.
    Unknown
    {beta}1 Modifies BK Channel Activation [Protein Structure and Folding] (2014)
    The American Society for Biochemistry and Molecular Biology (ASBMB)
    Details
    Publication Date: 2014-06-14
    Description: Large conductance Ca2+- and voltage-activated potassium (BK) channels, composed of pore-forming α subunits and auxiliary β subunits, play important roles in diverse physiological activities. The β1 is predominately expressed in smooth muscle cells, where it greatly enhances the Ca2+ sensitivity of BK channels for proper regulation of smooth muscle tone. However, the structural basis underlying dynamic interaction between BK mSlo1 α and β1 remains elusive. Using macroscopic ionic current recordings in various Ca2+ and Mg2+ concentrations, we identified two binding sites on the cytosolic N terminus of β1, namely the electrostatic enhancing site (mSlo1(K392,R393)-β1(E13,T14)), increasing the calcium sensitivity of BK channels, and the hydrophobic site (mSlo1(L906,L908)-β1(L5,V6,M7)), passing the physical force from the Ca2+ bowl onto the enhancing site and S6 C-linker. Dynamic binding of these sites affects the interaction between the cytosolic domain and voltage-sensing domain, leading to the reduction of Mg2+ sensitivity. A comprehensive structural model of the BK(mSlo1 α-β1) complex was reconstructed based on these functional studies, which provides structural and mechanistic insights for understanding BK gating.
    Print ISSN: 0021-9258
    Electronic ISSN: 1083-351X
    Topics: Biology , Chemistry and Pharmacology
    Published by The American Society for Biochemistry and Molecular Biology (ASBMB)
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 8
    facet.materialart.
    Unknown
    T Cell Ig Mucin-3 Promotes Homeostasis of Sepsis by Negatively Regulating the TLR Response [IMMUNE REGULATION] (2013)
    The American Association of Immunologists (AAI)
    Details
    Publication Date: 2013-02-16
    Description: Sepsis is an excessive inflammatory condition with a high mortality rate and limited prediction and therapeutic options. In this study, for the first time, to our knowledge, we found that downregulation and/or blockade of T cell Ig and mucin domain protein 3 (Tim-3), a negative immune regulator, correlated with severity of sepsis, suggesting that Tim-3 plays important roles in maintaining the homeostasis of sepsis in both humans and a mouse model. Blockade and/or downregulation of Tim-3 led to increased macrophage activation, which contributed to the systemic inflammatory response in sepsis, whereas Tim-3 overexpression in macrophages significantly suppressed TLR-mediated proinflammatory cytokine production, indicating that Tim-3 is a negative regulator of TLR-mediated immune responses. Cross-talk between the Tim-3 and TLR4 pathways makes TLR4 an important contributor to Tim-3–mediated negative regulation of the innate immune response. Tim-3 signaling inhibited LPS–TLR4–mediated NF-B activation by increasing PI3K–AKT phosphorylation and A20 activity. This negative regulatory role of Tim-3 reflects a new adaptive compensatory and protective mechanism in sepsis victims, a finding of potential importance for modulating innate responses in these patients.
    Print ISSN: 0022-1767
    Electronic ISSN: 1550-6606
    Topics: Medicine
    Published by The American Association of Immunologists (AAI)
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 9
    facet.materialart.
    Unknown
    CUTL1 Regulates Drug Resistance in Gastric Cancer [Cell Biology] (2013)
    The American Society for Biochemistry and Molecular Biology (ASBMB)
    Details
    Publication Date: 2013-02-09
    Description: Gastric cancer is one of the leading causes of malignancy-related mortality worldwide, and drug resistance hampered the clinical efficacy of chemotherapy. To better understand the molecular mechanism causing drug resistance, we previously established an isogenic pair of doxorubicin-sensitive and -resistant gastric cancer cell lines, SGC7901 and SGC7901/ADR cells. Here, we investigated how modulation of CUTL1 activity affects the response of gastric cancer to frequently used chemotherapeutic agents. In this study, we demonstrated that CUTL1 transcription activity was significantly reduced in doxorubicin-resistant cells. Furthermore, decreased CUTL1 expression was strongly associated with intrinsic drug resistance in human gastric cancer tissues and could be used as a poor prognosis biomarker. Both gain-of-function (by overexpression of active CUTL1) and loss-of-function (by CUTL1-specific shRNA knockdown) studies showed that increased CUTL1 activity significantly enhanced cell sensitivity to drugs and led to increased apoptosis, whereas decreased CUTL1 expression dramatically reduced cell sensitivity to drugs and thus fewer apoptoses. Importantly, modulation of CUTL1 activity resulted in altered sensitivity to multiple drugs. In vivo mouse studies indicated that overexpression of active CUTL1 significantly resulted in increased cancer tissue response to chemotherapy and therefore inhibited growth, whereas knockdown of CUTL1 conferred resistance to chemotherapy. Taken together, our results strongly indicate that CUTL1 activity is inversely associated with drug resistance and thus is an attractive therapeutic target to modulate multidrug resistance in gastric cancer.
    Print ISSN: 0021-9258
    Electronic ISSN: 1083-351X
    Topics: Biology , Chemistry and Pharmacology
    Published by The American Society for Biochemistry and Molecular Biology (ASBMB)
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 10
    facet.materialart.
    Unknown
    Cutting Edge: Lymphotoxin Signaling Is Essential for Clearance of Salmonella from the Gut Lumen and Generation of Anti-Salmonella Protective Immunity [CUTTING EDGE] (2016)
    The American Association of Immunologists (AAI)
    Details
    Publication Date: 2016-12-20
    Description: The immunological components that control resolution of Salmonella infection and successful vaccination are poorly defined. In a model of chronic gastrointestinal infection, we observed that the lymphotoxin (LT) pathway is essential for the clearance and resolution of primary infection of attenuated Salmonella enterica Typhimurium strain SL3261 aroA . Using gnotobiotic mice, we show that LTβ receptor (LTβR) signaling and the microbiota are required to promote clearance of attenuated S. enterica Typhimurium from the gut lumen. We also found that LTβR signaling was required for successful immunization and subsequent protection upon challenge with a virulent strain of S . enterica Typhimurium. LTβR signaling promoted the development of specific IgG recognizing S . enterica Typhimurium during infection, as well as Ag-driven IFN- responses. B cell– and type 3 innate lymphoid cell–derived LT signaling, but not T cell–derived LT, contributes to anti– S . enterica Typhimurium protective responses. Collectively, our results suggest that LT signaling is essential for multiple steps of anti– S . enterica Typhimurium immune responses.
    Print ISSN: 0022-1767
    Electronic ISSN: 1550-6606
    Topics: Medicine
    Published by The American Association of Immunologists (AAI)
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...