scholarly journals Identification of a novel effector domain of BIN1 for cancer suppression

2011 ◽  
Vol 112 (10) ◽  
pp. 2992-3001 ◽  
Author(s):  
Greta L. Lundgaard ◽  
Natae E. Daniels ◽  
Slovénie Pyndiah ◽  
Erica K. Cassimere ◽  
Kazi M. Ahmed ◽  
...  
Keyword(s):  
Effector Domain ◽  
Cancer Suppression

scholarly journals Extract of Pogostemon cablin Possesses Potent Anticancer Activity against Colorectal Cancer Cells In Vitro and In Vivo

2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Ju-Huei Chien ◽  
Shan-Chih Lee ◽  
Kai-Fu Chang ◽  
Xiao-Fan Huang ◽  
Yi-Ting Chen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Apoptosis ◽  
Cycle Arrest ◽  
Anticancer Effects ◽  
Pogostemon Cablin ◽  
Colorectal Cancer Cells ◽  
Potential Applicability ◽  
Cancer Suppression

Pogostemon cablin (PCa), an herb used in traditional Chinese medicine, is routinely used in the amelioration of different types of gastrointestinal discomfort. However, the mechanisms underlying the cancer suppression activity of PCa in colorectal cancer (CRC) cells have yet to be clarified. The aim of this study was to investigate the anticancer effects of PCa, specifically the induction of apoptosis in CRC cells. The growth inhibition curve of CRC cells following exposure to PCa was detected by an MTT assay. Moreover, PCa combined with 5-FU revealed a synergic effect of decreased cell viability. PCa inhibited cell proliferation and induced cell cycle arrest at the G0/G1 phase and cell apoptosis through regulation of associated protein expression. An in vivo study showed that PCa suppressed the growth of CRC via induction of cell apoptosis with no significant change in body weight or organ histology. Our results demonstrated that PCa inhibits the growth of CRC cells and induces apoptosis in vitro and in vivo, which suggests the potential applicability of PCa as an anticancer agent.

scholarly journals Muropeptide Binding and the X-ray Structure of the Effector Domain of the Transcriptional Regulator AmpR ofPseudomonas aeruginosa

2017 ◽  
Vol 139 (4) ◽  
pp. 1448-1451 ◽  
Author(s):  
David A. Dik ◽  
Teresa Domínguez-Gil ◽  
Mijoon Lee ◽  
Dusan Hesek ◽  
Byungjin Byun ◽  
...  
Keyword(s):  
Transcriptional Regulator ◽  
Effector Domain ◽  
X Ray

scholarly journals The Effector Domain of Myristoylated Alanine-rich C Kinase Substrate Binds Strongly to Phosphatidylinositol 4,5-Bisphosphate

2000 ◽  
Vol 276 (7) ◽  
pp. 5012-5019 ◽  
Author(s):  
Jiyao Wang ◽  
Anna Arbuzova ◽  
Gyöngyi Hangyás-Mihályné ◽  
Stuart McLaughlin
Keyword(s):  
Effector Domain ◽  
Kinase Substrate

scholarly journals Mechanism of N-Wasp Activation by Cdc42 and Phosphatidylinositol 4,5-Bisphosphate

2000 ◽  
Vol 150 (6) ◽  
pp. 1299-1310 ◽  
Author(s):  
Rajat Rohatgi ◽  
Hsin-yi Henry Ho ◽  
Marc W. Kirschner
Keyword(s):  
Binding Site ◽  
Physical Interaction ◽  
Regulatory Interaction ◽  
Actin Nucleation ◽  
Sequence Element ◽  
Effector Domain ◽  
Nucleation Activity ◽  
Syndrome Protein ◽  
Upstream Regulators ◽  
Terminal Effector

Neuronal Wiskott-Aldrich Syndrome protein (N-WASP) transmits signals from Cdc42 to the nucleation of actin filaments by Arp2/3 complex. Although full-length N-WASP is a weak activator of Arp2/3 complex, its activity can be enhanced by upstream regulators such as Cdc42 and PI(4,5)P2. We dissected this activation reaction and found that the previously described physical interaction between the NH2-terminal domain and the COOH-terminal effector domain of N-WASP is a regulatory interaction because it can inhibit the actin nucleation activity of the effector domain by occluding the Arp2/3 binding site. This interaction between the NH2- and COOH termini must be intramolecular because in solution N-WASP is a monomer. Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) influences the activity of N-WASP through a conserved basic sequence element located near the Cdc42 binding site rather than through the WASp homology domain 1. Like Cdc42, PI(4,5)P2 reduces the affinity between the NH2- and COOH termini of the molecule. The use of a mutant N-WASP molecule lacking this basic stretch allowed us to delineate a signaling pathway in Xenopus extracts leading from PI(4,5)P2 to actin nucleation through Cdc42, N-WASP, and Arp2/3 complex. In this pathway, PI(4,5)P2 serves two functions: first, as an activator of N-WASP; and second, as an indirect activator of Cdc42.

scholarly journals Sequestration of phosphoinositides by mutated MARCKS effector domain inhibits stimulated Ca2+mobilization and degranulation in mast cells

2011 ◽  
Vol 22 (24) ◽  
pp. 4908-4917 ◽  
Author(s):  
Deepti Gadi ◽  
Alice Wagenknecht-Wiesner ◽  
David Holowka ◽  
Barbara Baird
Keyword(s):  
Plasma Membrane ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Time Course ◽  
Fluorescent Protein ◽  
Immunoglobulin E ◽  
Dependent Manner ◽  
Effector Domain ◽  
Granule Exocytosis ◽  
Kinase C

Protein kinase C β (PKCβ) participates in antigen-stimulated mast cell degranulation mediated by the high-affinity receptor for immunoglobulin E, FcεRI, but the molecular basis is unclear. We investigated the hypothesis that the polybasic effector domain (ED) of the abundant intracellular substrate for protein kinase C known as myristoylated alanine-rich protein kinase C substrate (MARCKS) sequesters phosphoinositides at the inner leaflet of the plasma membrane until MARCKS dissociates after phosphorylation by activated PKC. Real-time fluorescence imaging confirms synchronization between stimulated oscillations of intracellular Ca2+concentrations and oscillatory association of PKCβ–enhanced green fluorescent protein with the plasma membrane. Similarly, MARCKS-ED tagged with monomeric red fluorescent protein undergoes antigen-stimulated oscillatory dissociation and rebinding to the plasma membrane with a time course that is synchronized with reversible plasma membrane association of PKCβ. We find that MARCKS-ED dissociation is prevented by mutation of four serine residues that are potential sites of phosphorylation by PKC. Cells expressing this mutated MARCKS-ED SA4 show delayed onset of antigen-stimulated Ca2+mobilization and substantial inhibition of granule exocytosis. Stimulation of degranulation by thapsigargin, which bypasses inositol 1,4,5-trisphosphate production, is also substantially reduced in the presence of MARCKS-ED SA4, but store-operated Ca2+entry is not inhibited. These results show the capacity of MARCKS-ED to regulate granule exocytosis in a PKC-dependent manner, consistent with regulated sequestration of phosphoinositides that mediate granule fusion at the plasma membrane.

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