Cell death regulation by B-cell lymphoma protein

Verma, Yogesh Kumar; Gangenahalli, Gurudutta; Singh, Vimal Kishor; Gupta, Pallavi; Chandra, Ramesh; Sharma, Rakesh Kumar; Raj, Hanumantharao G.

doi:10.1007/s10495-006-5702-1

Cited by 27 publications

(24 citation statements)

References 85 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…16 It is now known that antagonizing Bcl-2 function may lead to death in many types of cancer cells. 17 We observed that in DLA cells, Bcl-2 was highly overexpressed.…”

Section: Discussionmentioning

confidence: 99%

Phyllanthus amarus Inhibits Cell Growth and Induces Apoptosis in Dalton's Lymphoma Ascites Cells Through Activation of Caspase-3 and Downregulation of Bcl-2

Harikumar

Kuttan

2009

Integr Cancer Ther

View full text Add to dashboard Cite

show abstract

“…16 It is now known that antagonizing Bcl-2 function may lead to death in many types of cancer cells. 17 We observed that in DLA cells, Bcl-2 was highly overexpressed.…”

Section: Discussionmentioning

confidence: 99%

Phyllanthus amarus Inhibits Cell Growth and Induces Apoptosis in Dalton's Lymphoma Ascites Cells Through Activation of Caspase-3 and Downregulation of Bcl-2

Harikumar

Kuttan

2009

Integr Cancer Ther

View full text Add to dashboard Cite

show abstract

“…The activation and regulation of this suicide program involves numerous intra-and extra-cellular signals and factors [54][55][56]. Induction of apoptosis frequently requires the activation of the "initiator" caspases-2, -8 and -9 [57].…”

Section: Rch Response Protects Cells Against Cold-induced Apoptosismentioning

confidence: 99%

Rapid cold-hardening protects Drosophila melanogaster from cold-induced apoptosis

2007

View full text Add to dashboard Cite

The rapid cold-hardening (RCH) response increases the cold tolerance of insects by protecting against non-freezing, cold-shock injury. Apoptosis, or programmed cell death, plays important roles in development and the elimination of sub-lethally damaged cells. Our objectives were to determine whether apoptosis plays a role in cold-shock injury and, if so, whether the RCH response protects against cold-induced apoptosis in Drosophila melanogaster. The present study confirmed that RCH increased the cold tolerance of the adults at the organismal level. No flies in the cold-shocked group survived direct exposure to 7 degrees C for 2 h, whereas significantly more flies in the RCH group survived exposure to 7 degrees C for 2 h after a 2-h exposure to 5 degrees C. We used a TUNEL assay to detect and quantify apoptotic cell death in five groups of flies including control, cold-shocked, RCH, heat-shocked (37.5 degrees C, 30 min), and frozen (20 degrees C, 24 h) and found that apoptosis was induced by cold shock, heat shock, and freezing. The RCH treatment significantly improved cell viability by 38% compared to the cold-shocked group. Cold shock-induced DNA fragmentation shown by electrophoresis provided further evidence for apoptosis. SDS-PAGE analysis revealed an RCH-specific protein band with molecular mass of approximately 150 kDa. Western-blotting revealed three proteins that play key roles in the apoptotic pathway: caspase-9-like (apoptotic initiator), caspase-3-like (apoptotic executioner) and Bcl-2 (anti-apoptotic protein). Consequently, the results of this study support the hypothesis that the RCH response protects against cold-shock-induced apoptosis.

show abstract

“…Understanding the interactions of various proteins with FLD would likely help us to tweak apoptosis signaling and the treatment of various malignancies [12] in which Bcl-2 expression is not under control, such as acute myeloid leukemia (AML) [13]. Therefore, the FLD represents an attractive target for drugs that modulate protein-protein interactions, and studies of the FLD would likely facilitate drug discovery and improve our understanding of human diseases.…”

Section: Introductionmentioning

confidence: 99%

Molecular dynamics simulations of the Bcl-2 protein to predict the structure of its unordered flexible loop domain

2011

View full text Add to dashboard Cite

B-cell lymphoma (Bcl-2) protein is an anti-apoptotic member of the Bcl-2 family. It is functionally demarcated into four Bcl-2 homology (BH) domains: BH1, BH2, BH3, BH4, one flexible loop domain (FLD), a transmembrane domain (TM), and an X domain. Bcl-2's BH domains have clearly been elucidated from a structural perspective, whereas the conformation of FLD has not yet been predicted, despite its important role in regulating apoptosis through its interactions with JNK-1, PKC, PP2A phosphatase, caspase 3, MAP kinase, ubiquitin, PS1, and FKBP38. Many important residues that regulate Bcl-2 anti-apoptotic activity are present in this domain, for example Asp34, Thr56, Thr69, Ser70, Thr74, and Ser87. The structural elucidation of the FLD would likely help in attempts to accurately predict the effect of mutating these residues on the overall structure of the protein and the interactions of other proteins in this domain. Therefore, we have generated an increased quality model of the Bcl-2 protein including the FLD through modeling. Further, molecular dynamics (MD) simulations were used for FLD optimization, to predict the flexibility, and to determine the stability of the folded FLD. In addition, essential dynamics (ED) was used to predict the collective motions and the essential subspace relevant to Bcl-2 protein function. The predicted average structure and ensemble of MD-simulated structures were submitted to the Protein Model Database (PMDB), and the Bcl-2 structures obtained exhibited enhanced quality. This study should help to elucidate the structural basis for Bcl-2 anti-apoptotic activity regulation through its binding to other proteins via the FLD.

show abstract

Cell death regulation by B-cell lymphoma protein

Cited by 27 publications

References 85 publications

Phyllanthus amarus Inhibits Cell Growth and Induces Apoptosis in Dalton's Lymphoma Ascites Cells Through Activation of Caspase-3 and Downregulation of Bcl-2

Phyllanthus amarus Inhibits Cell Growth and Induces Apoptosis in Dalton's Lymphoma Ascites Cells Through Activation of Caspase-3 and Downregulation of Bcl-2

Rapid cold-hardening protects Drosophila melanogaster from cold-induced apoptosis

Molecular dynamics simulations of the Bcl-2 protein to predict the structure of its unordered flexible loop domain

Contact Info

Product

Resources

About