Inhibition of Tau Polymerization by Its Carboxy-Terminal Caspase Cleavage Fragment†

Biochemistry ◽  
2003 ◽  
Vol 42 (27) ◽  
pp. 8325-8331 ◽  
Author(s):  
R. W. Berry ◽  
A. Abraha ◽  
S. Lagalwar ◽  
N. LaPointe ◽  
T. C. Gamblin ◽  
...  
Keyword(s):  
Caspase Cleavage ◽  
Cleavage Fragment ◽  
Carboxy Terminal ◽  
Tau Polymerization

scholarly journals Expression of a naturally occurring angiotensin AT1 receptor cleavage fragment elicits caspase-activation and apoptosis

2011 ◽  
Vol 301 (5) ◽  
pp. C1175-C1185 ◽  
Author(s):  
Julia L. Cook ◽  
Akannsha Singh ◽  
Dawn deHaro ◽  
Jawed Alam ◽  
Richard N. Re
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Fold Increase ◽  
Muscle Cells ◽  
Cell Types ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Breast Adenocarcinoma ◽  
Protein Fusion ◽  
Cleavage Fragment ◽  
Carboxy Terminal

Several transmembrane receptors are documented to accumulate in nuclei, some as holoreceptors and others as cleaved receptor products. Our prior studies indicate that a population of the 7-transmembrane angiotensin type-1 receptor (AT1R) is cleaved in a ligand-augmented manner after which the cytoplasmic, carboxy-terminal cleavage fragment (CF) traffics to the nucleus. In the present report, we determine the precise cleavage site within the AT1R by mass spectrometry and Edman sequencing. Cleavage occurs between Leu(305) and Gly(306) at the junction of the seventh transmembrane domain and the intracellular cytoplasmic carboxy-terminal domain. To evaluate the function of the CF distinct from the holoreceptor, we generated a construct encoding the CF as an in-frame yellow fluorescent protein fusion. The CF accumulates in nuclei and induces apoptosis in CHO-K1 cells, rat aortic smooth muscle cells (RASMCs), MCF-7 human breast adenocarcinoma cells, and H9c2 rat cardiomyoblasts. All cell types show nuclear fragmentation and disintegration, as well as evidence for phosphotidylserine displacement in the plasma membrane and activated caspases. RASMCs specifically showed a 5.2-fold increase ( P < 0.001) in CF-induced active caspases compared with control and a 7.2-fold increase ( P < 0.001) in cleaved caspase-3 (Asp174). Poly(ADP-ribose)polymerase was upregulated 4.8-fold ( P < 0.001) in CF expressing cardiomyoblasts and colocalized with terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). CF expression also induces DNA laddering, the gold-standard for apoptosis in all cell types studied. CF-induced apoptosis, therefore, appears to be a general phenomenon as it is observed in multiple cell types including smooth muscle cells and cardiomyoblasts.

scholarly journals Delta-Peptide Is the Carboxy-Terminal Cleavage Fragment of the Nonstructural Small Glycoprotein sGP of Ebola Virus

Virology ◽  
1999 ◽  
Vol 265 (1) ◽  
pp. 164-171 ◽  
Author(s):  
Valentina A. Volchkova ◽  
Hans-Dieter Klenk ◽  
Viktor E. Volchkov
Keyword(s):  
Ebola Virus ◽  
Cleavage Fragment ◽  
Carboxy Terminal

scholarly journals A caspase cleavage fragment of p115 induces fragmentation of the Golgi apparatus and apoptosis

2002 ◽  
Vol 159 (4) ◽  
pp. 637-648 ◽  
Author(s):  
Raymond Chiu ◽  
Leonid Novikov ◽  
Shaeri Mukherjee ◽  
Dennis Shields
Keyword(s):  
Golgi Apparatus ◽  
Mammalian Cells ◽  
Resistant Mutant ◽  
Apoptotic Response ◽  
Caspase Cleavage ◽  
Vesicle Tethering ◽  
Cleavage Fragment ◽  
Resistant Form ◽  
Golgi Fragmentation

In mammalian cells, the Golgi apparatus undergoes extensive fragmentation during apoptosis. p115 is a key vesicle tethering protein required for maintaining the structural organization of the Golgi apparatus. Here, we demonstrate that p115 was cleaved during apoptosis by caspases 3 and 8. Compared with control cells expressing native p115, those expressing a cleavage-resistant form of p115 delayed Golgi fragmentation during apoptosis. Expression of cDNAs encoding full-length or an NH2-terminal caspase cleavage fragment of p115 had no effect on Golgi morphology. In contrast, expression of the COOH-terminal caspase cleavage product of p115 itself caused Golgi fragmentation. Furthermore, this fragment translocated to the nucleus and its expression was sufficient to induce apoptosis. Most significantly, in vivo expression of the COOH-terminal fragment in the presence of caspase inhibitors, or upon coexpression with a cleavage-resistant mutant of p115, showed that p115 degradation plays a key role in amplifying the apoptotic response independently of Golgi fragmentation.

Inhibition of Platelet Adhesion to Fibrin(ogen) in Flowing Whole Blood by Arg-Gly-Asp and Fibrinogen γ-Chain Carboxy Terminal Peptides

1992 ◽  
Vol 68 (06) ◽  
pp. 694-700 ◽  
Author(s):  
Roy R Hantgan ◽  
Silvia C Endenburg ◽  
I Cavero ◽  
Gérard Marguerie ◽  
André Uzan ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Whole Blood ◽  
Platelet Adhesion ◽  
Integrin Receptor ◽  
Shear Rates ◽  
Perfusion Chamber ◽  
Receptor Recognition ◽  
Adhesive Interactions ◽  
Coated Surfaces ◽  
Carboxy Terminal

SummaryWe have employed synthetic peptides with sequences corresponding to the integrin receptor-recognition regions of fibrinogen as inhibitors of platelet aggregation and adhesion to fibrinogen-and fibrin-coated surfaces in flowing whole blood, using a rectangular perfusion chamber at wall shear rates of 300 s–1 and 1,300 s–1. D-RGDW caused substantial inhibition of platelet aggregation and adhesion to fibrinogen and fibrin at both shear rates, although it was least effective at blocking platelet adhesion to fibrin at 300 s–1. RGDS was a weaker inhibitor, and produced a biphasic dose-response curve; SDRG was inactive. HHLGGAK-QAGDV partially inhibited platelet aggregation and adhesion to fibrin(ogen) at both shear rates. These results support the identification of an RGD-specific receptor, most likely the platelet integrin glycoprotein IIb: III a, as the primary receptor responsible for platelet: fibrin(ogen) adhesive interactions under flow conditions, and indicate that platelet adhesion to surface bound fibrin(ogen) is stabilized by multivalent receptor-ligand contacts.

The Ability of Fibrinogens, FI and FII, to Support ADP- Induced Platelet Aggregation

1983 ◽  
Vol 50 (02) ◽  
pp. 527-529 ◽  
Author(s):  
H M Phillips ◽  
A Mansouri ◽  
C A Perry
Keyword(s):  
Platelet Aggregation ◽  
Terminal Portion ◽  
Hepes Buffer ◽  
Carboxy Terminal

SummaryFibrinogen plays an integral part in ADP-induced platelet aggregation. Controversy exists in regard to the role of the carboxy termini of fibrinogen Aa chains in this reaction. We have attempted to clarify this problem in view of the availability of a highly purified FII fibrinogen fraction. Kabi fibrinogen or its purified fractions FI, FII and FIII-IV-V were added to washed platelets in the presence of Tyrode-HEPES buffer pH 7.4. Aggregation was initiated by the addition of calcium and ADP. These fibrinogen fractions equally promoted ADP-induced platelet aggregation. The major difference among these fractions is in their Aα chains. The FI fraction contains intact Aα chains while FII and FIH-IV-V fractions have one and two partially degraded Aα chains at the carboxy terminal portion respectively. We conclude that the carboxy terminal portion of the Aα chain does not play an important role in promoting ADP-induced platelet aggregation.

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