Dmp53 protects the Drosophila retina during a developmentally regulated DNA damage response

Jassim, Omar; Fink, Jill L.; Cagan, Ross L.

doi:10.1093/emboj/cdg543

Cited by 50 publications

(63 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This result is surprising, since notable, yet modest effects upon DIAP1 immunoreactivity are often observed in animal studies. [39][40][41][42][43] Reduced DIAP1 levels have also been documented in cultured Figure 7 Rpr expression does not suppress bulk translation in vivo. After Rpr-GFP and various fusion proteins were expressed for the indicated time, cells were labeled with 35 S-methionine for 20 min.…”

Section: Discussionmentioning

confidence: 91%

Bifunctional killing activity encoded by conserved reaper proteins

Chen

Shi

et al. 2004

Cell Death Differ

View full text Add to dashboard Cite

Drosophila activators of apoptosis mapping to the Reaper region function, in part, by antagonizing IAP proteins through a shared RHG motif. We isolated Reaper from the Blowfly L. cuprina, which triggered extensive apoptosis in Drosophila cells. Conserved regions of Reaper were tested in the context of GFP fusions and a second killing activity, distinct from the RHG, was identified. A 20 amino-acid peptide, designated R3, conferred targeting to a focal compartment and promoted membrane blebbing. Killing by the R3 fragment did not correlate with translational suppression or with reduced DIAP1 levels. Likewise, R3-induced cell deaths were only modestly suppressed by silencing of Dronc and involved no detectable association with DIAP1. Instead, a second IAPbinding domain, distinct from the R3, was identified at the C terminus of Reaper that bound to DIAP1 but failed to trigger apoptosis. Collectively, these findings are inconsistent with single effector models for cell killing by Reaper and suggest, instead, that Reaper encodes conserved bifunctional death activities that propagate through distinct effector pathways.

show abstract

Section: Discussionmentioning

confidence: 91%

Bifunctional killing activity encoded by conserved reaper proteins

Chen

Shi

et al. 2004

Cell Death Differ

View full text Add to dashboard Cite

show abstract

“…A recent example identified in flies is the genotoxic stress caused by UVC irradiation during pupal eye development ( Jassim et al 2003;Luo et al 2007). In the absence of photoreactivation-induced DNA repair, stimulation of JNK signaling by UVC at 24 hr after pupal formation promotes apoptosis, which leads to tissue loss in a dose-dependent manner.…”

Section: Resultsmentioning

confidence: 99%

The PP2C Alphabet Is a Negative Regulator of Stress-Activated Protein Kinase Signaling in Drosophila

et al. 2009

View full text Add to dashboard Cite

The Jun N-terminal kinase and p38 pathways, also known as stress-activated protein kinase (SAPK) pathways, are signaling conduits reiteratively used throughout the development and adult life of metazoans where they play central roles in the control of apoptosis, immune function, and environmental stress responses. We recently identified a Drosophila Ser/Thr phosphatase of the PP2C family, named Alphabet (Alph), which acts as a negative regulator of the Ras/ERK pathway. Here we show that Alph also plays an inhibitory role with respect to Drosophila SAPK signaling during development as well as under stress conditions such as oxidative or genotoxic stresses. Epistasis experiments suggest that Alph acts at a step upstream of the MAPKKs Hep and Lic. Consistent with this interpretation, biochemical experiments identify the upstream MAPKKKs Slpr, Tak1, and Wnd as putative substrates. Together with previous findings, this work identifies Alph as a general attenuator of MAPK signaling in Drosophila.

show abstract

“…S3), we tested whether overexpressed STAT92E was able to block apoptosis in the fast dividing cells of the first mitotic wave in the eye disc. These cells normally undergo rapid apoptosis when irradiated with x-rays (19,20) (Fig. 6Ab).…”

Section: Stat92ementioning

confidence: 99%

STAT92E is a positive regulator ofDrosophilainhibitor of apoptosis 1 (DIAP/1) and protects against radiation-induced apoptosis

Betz¹,

Ryoo

Steller

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The proapoptotic factors Reaper, Hid, Grim, and Sickle regulate apoptosis in Drosophila by inhibiting the antiapoptotic factor DIAP1 (Drosophila inhibitor of apoptosis 1). Heat, UV light, x-rays, and developmental signals can all increase the proapoptotic factors, but the control of transcription of the diap1 gene is unclear. We show that in imaginal discs the single Drosophila STAT protein (STAT92E) when activated can directly increase DIAP1 through binding to STAT DNA-binding sites in the diap1 promoter. The STAT92E contribution to DIAP1 production is required for cell survival after x-irradiation but not under unstressed conditions. Because DIAP1 prevents apoptosis after a variety of stresses, STAT92E may have a role in regulating stress responses in general.Jak STAT ͉ stress ͉ cancer ͉ survival T he regulation of apoptosis is highly conserved in animals and is thought to limit the risk of genomic instability and cancer. Its function depends on the balanced levels of proapoptotic and antiapoptotic proteins (1).The Drosophila proapoptotic factors Reaper, Hid, Grim, and Sickle [also called IAP-binding motif (IBM) proteins] are specifically increased by a variety of agents, both intrinsic developmental signals and extrinsic events (e.g., heat, UV, and ionizing radiation) (2). Inhibition by the IBM proteins of the antiapoptotic activity of DIAP1 (Drosophila inhibitor of apoptosis 1) (3, 4) releases Dronc (the Drosophila caspase 9 ortholog) and drice/dcp1 (caspase 3 ortholog), triggering apoptosis. Proteinprotein interactions of DIAP1 with the IBM proteins and with caspases have received extensive examination (2, 5). However, to our knowledge, direct transcriptional regulation by specific transcription factor(s) of the widely expressed diap1 gene has not been described.Two of the seven human STAT family members are antiapoptotic and their overactivity is correlated with cancer, heightening the previously unrecognized antiapoptotic role of STAT92E. The simpler Jak-STAT pathway in Drosophila consists of the ligands unpaired 1, 2, and 3 and the receptor domeless, with which one Jak family kinase, hopscotch, is associated. Mutations in the pathway affect a wide variety of processes including a positive effect on the cell cycle (6-8).We now report that the full-length tyrosine-phosphorylated STAT92E isoform participates in blocking apoptosis in vivo by acting through highly conserved STAT DNA-binding sites in the diap1 promoter to maintain normal DIAP1 levels. In developing eye and wing discs, STAT92E, although not critical for maintaining basal levels of DIAP1 for survival under unstressed conditions, increases DIAP1 to levels required to combat stressinduced apoptosis.

show abstract

Dmp53 protects the Drosophila retina during a developmentally regulated DNA damage response

Cited by 50 publications

References 56 publications

Bifunctional killing activity encoded by conserved reaper proteins

Bifunctional killing activity encoded by conserved reaper proteins

The PP2C Alphabet Is a Negative Regulator of Stress-Activated Protein Kinase Signaling in Drosophila

STAT92E is a positive regulator ofDrosophilainhibitor of apoptosis 1 (DIAP/1) and protects against radiation-induced apoptosis

Contact Info

Product

Resources

About