Drosophila IAP1-mediated ubiquitylation controls activation of the initiator caspase DRONC independent of protein degradation

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Drosophila IAP1-mediated ubiquitylation controls activation of the initiator caspase DRONC independent of protein degradation. / Lee, Tom V; Fan, Yun; Wang, Shiuan; Srivastava, Mayank; Broemer, Meike; Meier, Pascal; Bergmann, Andreas.

In: PLoS Genetics, Vol. 7, No. 9, 2011, p. e1002261.

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Lee, Tom V ; Fan, Yun ; Wang, Shiuan ; Srivastava, Mayank ; Broemer, Meike ; Meier, Pascal ; Bergmann, Andreas. / Drosophila IAP1-mediated ubiquitylation controls activation of the initiator caspase DRONC independent of protein degradation. In: PLoS Genetics. 2011 ; Vol. 7, No. 9. pp. e1002261.

Bibtex

@article{60556ebf269b4aca9a06c0e2d353f994,
title = "Drosophila IAP1-mediated ubiquitylation controls activation of the initiator caspase DRONC independent of protein degradation",
abstract = "Ubiquitylation targets proteins for proteasome-mediated degradation and plays important roles in many biological processes including apoptosis. However, non-proteolytic functions of ubiquitylation are also known. In Drosophila, the inhibitor of apoptosis protein 1 (DIAP1) is known to ubiquitylate the initiator caspase DRONC in vitro. Because DRONC protein accumulates in diap1 mutant cells that are kept alive by caspase inhibition ({"}undead{"} cells), it is thought that DIAP1-mediated ubiquitylation causes proteasomal degradation of DRONC, protecting cells from apoptosis. However, contrary to this model, we show here that DIAP1-mediated ubiquitylation does not trigger proteasomal degradation of full-length DRONC, but serves a non-proteolytic function. Our data suggest that DIAP1-mediated ubiquitylation blocks processing and activation of DRONC. Interestingly, while full-length DRONC is not subject to DIAP1-induced degradation, once it is processed and activated it has reduced protein stability. Finally, we show that DRONC protein accumulates in {"}undead{"} cells due to increased transcription of dronc in these cells. These data refine current models of caspase regulation by IAPs.",
author = "Lee, {Tom V} and Yun Fan and Shiuan Wang and Mayank Srivastava and Meike Broemer and Pascal Meier and Andreas Bergmann",
year = "2011",
doi = "10.1371/journal.pgen.1002261",
language = "English",
volume = "7",
pages = "e1002261",
journal = "PLoS Genetics",
issn = "1553-7390",
publisher = "Public Library of Science (PLOS)",
number = "9",

}

RIS

TY - JOUR

T1 - Drosophila IAP1-mediated ubiquitylation controls activation of the initiator caspase DRONC independent of protein degradation

AU - Lee, Tom V

AU - Fan, Yun

AU - Wang, Shiuan

AU - Srivastava, Mayank

AU - Broemer, Meike

AU - Meier, Pascal

AU - Bergmann, Andreas

PY - 2011

Y1 - 2011

N2 - Ubiquitylation targets proteins for proteasome-mediated degradation and plays important roles in many biological processes including apoptosis. However, non-proteolytic functions of ubiquitylation are also known. In Drosophila, the inhibitor of apoptosis protein 1 (DIAP1) is known to ubiquitylate the initiator caspase DRONC in vitro. Because DRONC protein accumulates in diap1 mutant cells that are kept alive by caspase inhibition ("undead" cells), it is thought that DIAP1-mediated ubiquitylation causes proteasomal degradation of DRONC, protecting cells from apoptosis. However, contrary to this model, we show here that DIAP1-mediated ubiquitylation does not trigger proteasomal degradation of full-length DRONC, but serves a non-proteolytic function. Our data suggest that DIAP1-mediated ubiquitylation blocks processing and activation of DRONC. Interestingly, while full-length DRONC is not subject to DIAP1-induced degradation, once it is processed and activated it has reduced protein stability. Finally, we show that DRONC protein accumulates in "undead" cells due to increased transcription of dronc in these cells. These data refine current models of caspase regulation by IAPs.

AB - Ubiquitylation targets proteins for proteasome-mediated degradation and plays important roles in many biological processes including apoptosis. However, non-proteolytic functions of ubiquitylation are also known. In Drosophila, the inhibitor of apoptosis protein 1 (DIAP1) is known to ubiquitylate the initiator caspase DRONC in vitro. Because DRONC protein accumulates in diap1 mutant cells that are kept alive by caspase inhibition ("undead" cells), it is thought that DIAP1-mediated ubiquitylation causes proteasomal degradation of DRONC, protecting cells from apoptosis. However, contrary to this model, we show here that DIAP1-mediated ubiquitylation does not trigger proteasomal degradation of full-length DRONC, but serves a non-proteolytic function. Our data suggest that DIAP1-mediated ubiquitylation blocks processing and activation of DRONC. Interestingly, while full-length DRONC is not subject to DIAP1-induced degradation, once it is processed and activated it has reduced protein stability. Finally, we show that DRONC protein accumulates in "undead" cells due to increased transcription of dronc in these cells. These data refine current models of caspase regulation by IAPs.

U2 - 10.1371/journal.pgen.1002261

DO - 10.1371/journal.pgen.1002261

M3 - Article

C2 - 21909282

VL - 7

SP - e1002261

JO - PLoS Genetics

JF - PLoS Genetics

SN - 1553-7390

IS - 9

ER -