Instruct: Identify the main category of Biorxiv papers based on the titles and abstracts
Query: Cell-to-cell heterogeneities during extrinsic apoptosis arise from cell cycle progression and transmitotic apoptosis resistance Extrinsic apoptosis relies on TNF-family receptor activation by immune cells or receptor-activating biologics. Here, we monitored cell cycle progression at minutes resolution to relate apoptosis kinetics and cell-to-cell heterogeneities in death decisions to cell cycle phases. Interestingly, we found that cells in S phase delay TRAIL receptor-induced death in favour for mitosis, thereby passing on an apoptosis-primed state to their offspring. This translates into two distinct fates, apoptosis execution post mitosis or cell survival from inefficient apoptosis. Transmitotic resistance is linked to Mcl-1 upregulation from mid S phase onwards, which allows cells to pass through mitosis with activated caspase-8, and with cells escaping apoptosis after mitosis sustaining sublethal DNA damage. Antagonizing Mcl-1 by BH3-mimetics suppresses cell cycle-dependent delays in apoptosis, prevents apoptosis-resistant progression through mitosis and averts unwanted survival from apoptosis induction. Cell cycle progression therefore modulates signal transduction during extrinsic apoptosis, with Mcl-1 governing decision making between death, proliferation and survival from inefficient apoptosis induction. Cell cycle progression thus is a crucial process from which cell-to-cell heterogeneities in fates and treatment outcomes emerge in isogenic cell populations during extrinsic apoptosis signalling.
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The categories of this paper are: neuroscience
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The categories of this paper are: and
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The categories of this paper are: synthetic
15
The categories of this paper are: developmental
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The categories of this paper are: pharmacology
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The categories of this paper are: communication
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The categories of this paper are: evolutionary
30
The categories of this paper are: scientific
12
The categories of this paper are: behavior
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The categories of this paper are: cancer
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The categories of this paper are: plant
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The categories of this paper are: zoology
31
The categories of this paper are: paleontology
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The categories of this paper are: pathology
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The categories of this paper are: bioengineering
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The categories of this paper are: animal