Specific allosteric inhibition of the IREα RNase (unfolded protein response pt.II)

from For the sake of reproducibility - a technical replicate by Tumor Necrosis Factor-alpha

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lyrics

Identification of key players in determining cell viability and tumor proliferation
In the context of endoplasmic reticulum stress that triggers the unfolded protein responses
A challenging endeavour / faced with many obstacles / not the least of which being the elucidation
Of precise molecular pathways / involved in tumorigenesis / and cellular proliferation

Blocking the active domain – specific allosteric inhibition
Promoting cell survival – specific allosteric inhibition

Accumulation of unfolded proteins inducing homo-oligomerization
Of a particular kinase/RNase enzyme, splicing the XB1 transcription factor
Abnormal immune system activity / and cellular stress responses / threshold level in substrate degradation
Kinase-inhibiting / RNase attenuators / disrupting oligomerization

Blocking the active domain – specific allosteric inhibition
Promoting cell survival – specific allosteric inhibition

IREalpha unfolded protein sensor, an ineffective target to block the growth of tumors
Tumor cell survival unscathed by the inhibition of the endonuclease domain of this particular transmembrane sensor

Blocking the active domain - specific allosteric inhibition
Promoting cell survival - specific allosteric inhibition
Unfolded protein responses in stress-induced degeneration
Cellular fate under control of small-molecule allosteric modulation

Ref: Ghosh R et al. ”Allosteric Inhibition of the IRE1α RNase Preserves Cell Viability and Function during Endoplasmic Reticulum Stress.” Cell Vol. 158, Iss. 3 pp534-548 (2014)

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from For the sake of reproducibility - a technical replicate, released January 24, 2018

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Tumor Necrosis Factor-alpha Neuville, Québec

Scientists, academics, gorefiends and grindheads of the world rejoice: Tumor Necrosis Factor-alpha unleashes its take on full blown Carcass-worship, topped with unique lyrical themes inspired by the most recent knowledge in state-of-the-art scientific research from the fields of cellular and molecular biology. ... more

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