GSK3β‑mediated Ser156 phosphorylation modulates a BH3‑like domain in BCL2L12 during TMZ‑induced apoptosis and autophagy in glioma cells

International Journal of Molecular Medicine
Cheng-Wei ChuYi-Ren Hong

Abstract

BH3 domains, classified initially as BCL2 homology domains, participate in both apoptosis and autophagy. Beclin‑1 contains a BH3 domain, which is required for binding to antiapoptotic BCL2 homologs and BCL2‑mediated inhibition of autophagy. BCL2‑like 12 (BCL2L12) also harbors a BH3‑like domain, which is 12 residues long and contains a LXXXAE/D motif. In a yeast two‑hybrid system performed in the present study, BCL2L12 shared similar binding partnerships to antiapoptotic BCL2 homologs, such as Beclin‑1. In addition, this BH3‑like domain was involved in anti‑apoptosis and drug‑induced autophagy in glioma cell lines. Mutations in S156 and hydrophobic L213 to alanine counteracted the antiapoptotic properties of BCL2L12 and downregulated the activation of microtubule associated protein 1 light chain 3B (LC3B), autophagy‑related (ATG)12‑ATG5 conjugates and Beclin‑1, compared with a BCL2L12 wild‑type group. Molecular dynamics simulations revealed that phosphorylation at Ser156 of BCL2L12 (within α‑6 and α‑7 helices) influenced the BH3‑like domain conformation (α‑9 helix), indicating that glycogen synthase kinase (GSK) 3β‑mediated Ser156 phosphorylation modulated a BH3‑like domain in BCL2L12. Altogether, the present findings indicated ...Continue Reading

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Citations

Sep 20, 2018·International Journal of Molecular Sciences·Paola PalumboBenedetta Cinque

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Methods Mentioned

BETA
co-immunoprecipitation
two-hybrid
PCR
Protein Assay
X-ray
nuclear translocation

Software Mentioned

pmemd
SPSS
Sigma plot
ImageJ
Systat
AmberTools17
Amber

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