Janus-Faced PIDD: A Sensor for DNA Damage-Induced Cell Death or Survival?

McCoy, Francis; Eckard, Laura; Nutt, Leta K.

doi:10.1016/j.molcel.2012.08.019

Cited by 160 publications

(18 citation statements)

References 12 publications

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“…Triptolide is an active extract from a Chinese herb Tripterygium wilfordii . Recent studies reveal that Triptolide enhances cancer cells sensitivity to chemotherapy drugs through apoptosis induction .…”

Section: Introductionmentioning

confidence: 99%

Triptolide sensitizes breast cancer cells to Doxorubicin through the DNA damage response inhibition

Deng

et al. 2018

Molecular Carcinogenesis

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Triptolide is an active component from a Chinese herb, Tripterygium wilfordii which has been applied for treating immune-related diseases over centuries. Recently, it was reported that a variety of cancer cell lines could be sensitized to DNA-damage based chemotherapy drugs in combination with Triptolide treatment. In the present study, we show that a short time exposure (3 h) to Triptolide, which did not trigger apoptosis, could specifically increase breast cancer cells sensitivity to Doxorubicin rather than other chemotherapy drugs including Paclitaxel, Fluorouracil, and Mitomycin C. Further studies revealed Triptolide downregulated ATM expression and inhibited DNA damage response to DNA double- strand breaks. Moreover, the chemosensitization effect to Doxorubicin from Triptolide was attenuated by overexpression of ATM in breast cancer cells. Our findings suggest that Triptolide specifically chemosensitizes breast cancer cells to Doxorubicin prior to apoptosis initiation through downregulating ATM expression and inhibiting DNA damage response.

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Section: Introductionmentioning

confidence: 99%

Triptolide sensitizes breast cancer cells to Doxorubicin through the DNA damage response inhibition

Deng

et al. 2018

Molecular Carcinogenesis

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“…In contrast to PIDD-C, PIDD-CC is thought to be pro-apoptotic. A previous study revealed that PIDD-CC was upregulated in the brain after irradiation [50][51][52][53] . Similarly, our study showed that PIDD-CC was significantly increased at 3 h after irradiation, which indicates that the roles of different PIDD segments differ in cell survival and apoptosis after irradiation, and NF-κB pathway activation precedes apoptosis.…”

Section: Histological and Immunohistochemical Examination Of Brain Timentioning

confidence: 93%

Shenqi Fuzheng Injection attenuates irradiation-induced brain injury in mice via inhibition of the NF-κB signaling pathway and microglial activation

et al. 2015

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“…This method aims to predict the values of the HDR assay for a given variant, which is a measure of the impact of this variant on BRCA1/2 molecular function. Because the output of the HDR assay is a continuous value, we opted for using an MLR as a modeling tool, as implemented in the python package Scikit-learn (Pedregosa et al, 2011). The LOOCV of the model was done with the same package.…”

Section: The Mlr Methodsmentioning

confidence: 99%

“…Here we have utilized the following: The confusion matrices, the accuracies per class, the overall accuracy, and the multiclass MCC (Gorodkin, 2004;Jurman, Riccadonna, & Furlanello, 2012). The multiclass MCC (Gorodkin, 2004;Jurman et al, 2012) was obtained using the implementation in the python package Scikit-learn (Pedregosa et al, 2011).…”

Section: Multiclass Performance Assessmentmentioning

confidence: 99%

BRCA1 ‐ and BRCA2 ‐specific in silico tools for variant interpretation in the CAGI 5 ENIGMA challenge

et al. 2019

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BRCA1 and BRCA2 (BRCA1/2) germline variants disrupting the DNA protective role of these genes increase the risk of hereditary breast and ovarian cancers. Correct identification of these variants then becomes clinically relevant, because it may increase the survival rates of the carriers. Unfortunately, we are still unable to systematically predict the impact of BRCA1/2 variants. In this article, we present a family of in silico predictors that address this problem, using a gene‐specific approach. For each protein, we have developed two tools, aimed at predicting the impact of a variant at two different levels: Functional and clinical. Testing their performance in different datasets shows that specific information compensates the small number of predictive features and the reduced training sets employed to develop our models. When applied to the variants of the BRCA1/2 (ENIGMA) challenge in the fifth Critical Assessment of Genome Interpretation (CAGI 5) we find that these methods, particularly those predicting the functional impact of variants, have a good performance, identifying the large compositional bias towards neutral variants in the CAGI sample. This performance is further improved when incorporating to our prediction protocol estimates of the impact on splicing of the target variant.

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Janus-Faced PIDD: A Sensor for DNA Damage-Induced Cell Death or Survival?

Abstract: In this issue of Molecular Cell, an activator of the PIDDosome (a complex comprising of PIDD, RAIDD, and caspase-2) is described in experiments detailing endogenous PIDDosome assembly and caspase-2 function after DNA damage in the presence of Chk1 suppression (Ando et al., 2012).

Cited by 160 publications

References 12 publications

Triptolide sensitizes breast cancer cells to Doxorubicin through the DNA damage response inhibition

Triptolide sensitizes breast cancer cells to Doxorubicin through the DNA damage response inhibition

Shenqi Fuzheng Injection attenuates irradiation-induced brain injury in mice via inhibition of the NF-κB signaling pathway and microglial activation

BRCA1 ‐ and BRCA2 ‐specific in silico tools for variant interpretation in the CAGI 5 ENIGMA challenge

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