How Do Hexokinases Inhibit Receptor-Mediated Apoptosis?
Abstract
:Simple Summary
Abstract
1. Pro-Apoptotic BCL-2 Activities Control the Molecular Decision to Apoptosis
2. Dynamic Retrotranslocation Determines the Effective BCL-2 Protein Pool
3. Membrane Receptors Guide the Function of BCL-2 Proteins by Activation of Downstream GTPases
GTPase Superfamily | Mode of Action |
---|---|
Ras | Raf-1-dependent phosphorylation of pro-apoptotic BAD/BIM [47,48,49] |
Ras binding to BCL-2, increasing its anti-apoptotic effect [54] | |
Activation of hexokinase I by K-Ras4A binding [55] | |
Rho | Rac-1 binding to BCL-2, increasing its anti-apoptotic effect [50] |
PAK-dependent phosphorylation of pro-apoptotic BAD by Rac/Cdc42 [50] |
4. Hexokinases: At the Crossroads between Glucose Metabolism and Apoptosis
5. Hexokinase-Dependent Retrotranslocation Protects Cells against Extrinsic Apoptosis
6. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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BCL-2 Family Member | Gene Name | Activity | Associated Diseases | Interacting BCL-2 Family Proteins in Cancer |
---|---|---|---|---|
BCL-2 | BCL2 | Anti-apoptotic | Follicular lymphoma 1, | BAX, BAD, BIM, tBID, PUMA |
high-grade B-cell lymphoma | ||||
BCL-xL | BCL2L1 | Anti-apoptotic | Absolute glaucoma, | BAX, BAK, BAD, BIM, tBID, PUMA |
tongue carcinoma | ||||
MCL-1 | MCL1 | Anti-apoptotic | Myeloid leukemia, | BAX, BAK, BIM, tBID, NOXA, PUMA |
chlamydia | ||||
BAX | BAX | Pro-apoptotic | T-cell acute lymphoblastic leukemia, | MCL-1, BFL-1, BCL-xL, BCL-2, BCL-w, |
colorectal cancer | BCL-B, PUMA, BIM, tBID | |||
BAK | BAK1 | Pro-apoptotic | Absolute glaucoma, | MCL-1, BFL-1, BCL-xL, PUMA, BIM, tBID |
keratoacanthoma | ||||
BID | BID | Pro-apoptotic | Bladder transitional cell papilloma, | MCL-1, BFL-1, BCL-xL, BCL-2, BCL-w, |
colon adenocarcinoma | BCL-B, BAX, BAK | |||
BIM | BCL2L11 | Pro-apoptotic | Interleukin-7 receptor alpha deficiency, | MCL-1, BFL-1, BCL-xL, BCL-2, BCL-w, |
lymphoproliferative syndrome | BCL-B, BAX, BAK | |||
BAD | BAD | Pro-apoptotic | B-cell lymphoma, | BCL-2, BCL-xL, BCL-w |
transient cerebral ischemia |
HK | Tissue Distribution | Subcellular Localization | Functions | Suggested Interactions in Cell Death Signaling | References |
---|---|---|---|---|---|
I | All mammalian tissues, | OMM, cytosol | Glucose catabolism, | BCL-xL | [56] |
main isoform in the brain | apoptosis regulator | BID | [56,57] * | ||
BIM | [56] | ||||
BAX | [56] | ||||
BAK | [56] | ||||
VDAC | [58,59] | ||||
II | Heart, skeletal muscle, | OMM, cytosol | Glucose catabolism, | BAX | [56,60] * |
adipose tissue | glycogen synthesis, | BAK | [56] | ||
apoptosis regulator | VDAC | [58,59] | |||
PKCε | [61] | ||||
AKT | [62] | ||||
PEA15 | [63] | ||||
TIGAR | [64] | ||||
III | Ubiquitously expressed at low levels, | Perinuclear | Glucose catabolism | ||
highest expression in lung, kidney | compartment | ||||
and liver | |||||
IV | Liver, pancreatic islets, certain | Cytosol | Glucose catabolism, | BAD | [65] |
parts of the brain and gut | intracellular glucose sensor | VDAC | [66] |
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Schoeniger, A.; Wolf, P.; Edlich, F. How Do Hexokinases Inhibit Receptor-Mediated Apoptosis? Biology 2022, 11, 412. https://doi.org/10.3390/biology11030412
Schoeniger A, Wolf P, Edlich F. How Do Hexokinases Inhibit Receptor-Mediated Apoptosis? Biology. 2022; 11(3):412. https://doi.org/10.3390/biology11030412
Chicago/Turabian StyleSchoeniger, Axel, Philipp Wolf, and Frank Edlich. 2022. "How Do Hexokinases Inhibit Receptor-Mediated Apoptosis?" Biology 11, no. 3: 412. https://doi.org/10.3390/biology11030412