scholarly journals Heck- and Suzuki-coupling approaches to novel hydroquinone inhibitors of calcium ATPase

2019 ◽  
Vol 15 ◽  
pp. 971-975 ◽  
Author(s):  
Robert J Kempton ◽  
Taylor A Kidd-Kautz ◽  
Soizic Laurenceau ◽  
Stefan Paula
Keyword(s):  
Prostate Cancer ◽  
Endoplasmic Reticulum ◽  
Natural Product ◽  
Suzuki Coupling ◽  
Calcium Atpase ◽  
Prostate Cancer Cells ◽  
Inhibitory Potency ◽  
Suitable Candidate ◽  
Endoplasmic Reticulum Calcium ◽  
Related Compounds

In this study, we explored Heck- and Suzuki-coupling methodology to modify the template 2,5-di-tert-butylhydroquinone (BHQ, 2), an inhibitor of the enzyme sarco/endoplasmic reticulum calcium ATPase (SERCA). We found that by utilizing Suzuki coupling, we could successfully attach a six-carbon tether to BHQ that terminated in a leucine moiety to obtain target 14. Similar to related compounds based on the structure of the natural product thapsigargin, 14 displayed inhibitory potency against SERCA activity. This makes 14 a suitable candidate for the future attachment of a deactivating peptide to convey specificity for prostate cancer cells.

scholarly journals δ‐Tocotrienol induces apoptosis, involving endoplasmic reticulum stress and autophagy, and paraptosis in prostate cancer cells

2019 ◽  
Vol 52 (3) ◽  
pp. e12576 ◽  
Author(s):  
Fabrizio Fontana ◽  
Roberta Manuela Moretti ◽  
Michela Raimondi ◽  
Monica Marzagalli ◽  
Giangiacomo Beretta ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Cancer Cells ◽  
Prostate Cancer Cells

scholarly journals Cytosolic Phosphorylation of Calnexin Controls Intracellular Ca2+ Oscillations via an Interaction with Serca2b

2000 ◽  
Vol 149 (6) ◽  
pp. 1235-1248 ◽  
Author(s):  
H. Llewelyn Roderick ◽  
James D. Lechleiter ◽  
Patricia Camacho
Keyword(s):  
Endoplasmic Reticulum ◽  
Xenopus Oocytes ◽  
Transmembrane Protein ◽  
Calcium Atpase ◽  
Site Directed Mutagenesis ◽  
Serine Residue ◽  
Endoplasmic Reticulum Calcium ◽  
Inositol 1,4,5 Trisphosphate ◽  
Functional Inhibition ◽  
Cytosolic Domain

Calreticulin (CRT) and calnexin (CLNX) are lectin chaperones that participate in protein folding in the endoplasmic reticulum (ER). CRT is a soluble ER lumenal protein, whereas CLNX is a transmembrane protein with a cytosolic domain that contains two consensus motifs for protein kinase (PK) C/proline- directed kinase (PDK) phosphorylation. Using confocal Ca2+ imaging in Xenopus oocytes, we report here that coexpression of CLNX with sarco endoplasmic reticulum calcium ATPase (SERCA) 2b results in inhibition of intracellular Ca2+ oscillations, suggesting a functional inhibition of the pump. By site-directed mutagenesis, we demonstrate that this interaction is regulated by a COOH-terminal serine residue (S562) in CLNX. Furthermore, inositol 1,4,5-trisphosphate– mediated Ca2+ release results in a dephosphorylation of this residue. We also demonstrate by coimmunoprecipitation that CLNX physically interacts with the COOH terminus of SERCA2b and that after dephosphorylation treatment, this interaction is significantly reduced. Together, our results suggest that CRT is uniquely regulated by ER lumenal conditions, whereas CLNX is, in addition, regulated by the phosphorylation status of its cytosolic domain. The S562 residue in CLNX acts as a molecular switch that regulates the interaction of the chaperone with SERCA2b, thereby affecting Ca2+ signaling and controlling Ca2+-sensitive chaperone functions in the ER.

scholarly journals Survival of Cancer Stem-Like Cells Under Metabolic Stress via CaMK2α-mediated Upregulation of Sarco/Endoplasmic Reticulum Calcium ATPase Expression

2017 ◽  
Vol 24 (7) ◽  
pp. 1677-1690 ◽  
Author(s):  
Ki Cheong Park ◽  
Seung Won Kim ◽  
Jeong Yong Jeon ◽  
A. Ra Jo ◽  
Hye Ji Choi ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Metabolic Stress ◽  
Calcium Atpase ◽  
Endoplasmic Reticulum Calcium
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