The ubiquitin ligase Itch mediates the antiapoptotic activity of epidermal growth factor by promoting the ubiquitylation and degradation of the truncated C‐terminal portion of Bid

Azakir, Bilal; Desrochers, Guillaume; Angers, Annie

doi:10.1111/j.1742-4658.2010.07562.x

Cited by 27 publications

(26 citation statements)

References 51 publications

(96 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In mammalian cells, ITCH depletion increased LATS1, a serine/threonine kinase in the Hippo pathway, enhancing FAS-induced apoptosis and reducing proliferation, survival, and migration [50]. This is consistent with results showing that in HEK-293T cells, ITCH depletion decreased cell survival and enhanced TRAIL-induced cell-death [51]. Increased cell death is thus a plausible explanation for loss of neuromasts in itchb morphants, but its assessment is difficult due to the recognized caveat in the use of MOs to examine apoptotic pathways [26].…”

Section: Discussionsupporting

confidence: 88%

Itch Is Required for Lateral Line Development in Zebrafish

Angers

Drapeau

2014

PLoS ONE

Self Cite

View full text Add to dashboard Cite

The zebrafish posterior lateral line is formed during early development by the deposition of neuromasts from a migrating primordium. The molecular mechanisms regulating the regional organization and migration of the primordium involve interactions between Fgf and Wnt/-catenin signaling and the establishment of specific cxcr4b and cxcr7b cytokine receptor expression domains. Itch has been identified as a regulator in several different signaling pathways, including Wnt and Cxcr4 signaling. We identified two homologous itch genes in zebrafish, itcha and itchb, with generalized expression patterns. By reducing itchb expression in particular upon morpholino knockdown, we demonstrated the importance of Itch in regulating lateral line development by perturbing the patterns of cxcr4b and cxcr7b expression. Itch knockdown results in a failure to down-regulate Wnt signaling and overexpression of cxcr4b in the primordium, slowing migration of the posterior lateral line primordium and resulting in abnormal development of the lateral line.

show abstract

Section: Discussionsupporting

confidence: 88%

Itch Is Required for Lateral Line Development in Zebrafish

Angers

Drapeau

2014

PLoS ONE

Self Cite

View full text Add to dashboard Cite

show abstract

“…38 The ubiquitin ligase Itch promotes the ubiquitylation and degradation of the truncated C-terminal portion of Bid, thus mediating the anti-apoptotic activity of epidermal growth factor. 39 Itch did not interact with full-length Bid, suggesting that it cannot be degraded through this pathway. 39 Of note, the N-terminal fragment of Bid generated by caspase cleavage can be also degraded in an ubiquitylation-dependent manner.…”

Section: Discussionmentioning

confidence: 92%

JNK1/2 regulate Bid by direct phosphorylation at Thr59 in response to ALDH1L1

et al. 2014

View full text Add to dashboard Cite

BH3 interacting-domain death agonist (Bid) is a BH3-only pro-apoptotic member of the Bcl-2 family of proteins. Its function in apoptosis is associated with the proteolytic cleavage to the truncated form tBid, mainly by caspase-8. tBid translocates to mitochondria and assists Bax and Bak in induction of apoptosis. c-Jun N-terminal kinase (JNK)-dependent alternative processing of Bid to jBid was also reported. We have previously shown that the folate stress enzyme 10-formyltetrahydrofolate dehydrogenase (ALDH1L1) activates JNK1 and JNK2 in cancer cells as a pro-apoptotic response. Here we report that in PC-3 prostate cancer cells, JNK1/2 phosphorylate Bid at Thr59 within the caspase cleavage site in response to ALDH1L1. In vitro, all three JNK isoforms, JNK 1–3, phosphorylated Thr59 of Bid with JNK1 being the least active. Thr59 phosphorylation protected Bid from cleavage by caspase-8, resulting in strong accumulation of the full-length protein and its translocation to mitochondria. Interestingly, although we did not observe jBid in response to ALDH1L1 in PC-3 cells, transient expression of Bid mutants lacking the caspase-8 cleavage site resulted in strong accumulation of jBid. Of note, a T59D mutant mimicking constitutive phosphorylation revealed more profound cleavage of Bid to jBid. JNK-driven Bid accumulation had a pro-apoptotic effect in our study: small interfering RNA silencing of either JNK1/2 or Bid prevented Bid phosphorylation and accumulation, and rescued ALDH1L1-expressing cells. As full-length Bid is a weaker apoptogen than tBid, we propose that the phosphorylation of Bid by JNKs, followed by the accumulation of the full-length protein, delays attainment of apoptosis, and allows the cell to evaluate the stress and make a decision regarding the response strategy. This mechanism perhaps can be modified by the alternative cleavage of phospho-T59 Bid to jBid at some conditions.

show abstract

“…F, the relative incorporation of HA-Lys-0 ubiquitin into immunoprecipitated FLAG-tagged YAP2 in HEK 293T cells co-expressing YFPtagged Amot130, Myc-tagged AIP4, mutant AIP4 (C830A), or control vectors was detected by immunoblot. G, the levels of total and ubiquitinated FLAG- thereby signaling the degradation of the transcription factor p73 (38) and the proapoptotic factor tBid (39). AIP4 also promotes cell proliferation by similarly inducing the degradation of LATS1 (25,40).…”

Section: Discussionmentioning

confidence: 99%