Expression of the Tumor Necrosis Factor Receptor-Associated Factors (TRAFs) 1 and 2 is a Characteristic Feature of Hodgkin and Reed-Sternberg Cells

Izban, Keith F.; Ergïn, Melek; Martinez, Robert L.; Alkan, Serhan

doi:10.1038/modpathol.3880243

Cited by 28 publications

(23 citation statements)

References 40 publications

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“…35 Although future studies are required to elucidate the precise mechanisms governing deregulation of these survival pathways in pediatric ALL, the role of other TRAF members in drug resistance has been suggested in several types of cancers, including B-cell chronic lymphoblastic leukemia (B-CLL) and Hodgkin disease. [47][48][49] We found that prolonged PARP1 activity contributed to the increase in NF-B transcriptional activity. Consequently, inhibiting PARP1 activity abolished NF-B DNA binding, leading to the down-regulation of its target proteins, cIAP1 and TRAF6, events that would facilitate p53-dependent apoptosis.…”

Section: Discussionmentioning

confidence: 87%

Apoptotic resistance to ionizing radiation in pediatric B-precursor acute lymphoblastic leukemia frequently involves increased NF-κB survival pathway signaling

Weston

Austen

Wei

et al. 2004

Blood

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To investigate possible causes of the variable response to treatment in pediatric B-precursor acute lymphoblastic leukemia (ALL) and to establish potential novel therapeutic targets, we used ionizing radiation (IR) exposure as a model of DNA damage formation to identify tumors with resistance to p53-dependent apoptosis. Twenty-one of 40 ALL tumors responded normally to IR, exhibiting accumulation of p53 and p21 proteins and cleavage of caspases 3, 7, and 9 and of PARP1. Nineteen tumors exhibited apoptotic resistance and lacked PARP1 and caspase cleavage; although 15 of these tumors had normal accumulation of p53 and p21 proteins, examples exhibited abnormal expression of TRAF5, TRAF6, and cIAP1 after IR, suggesting increased NF-B prosurvival signaling as the mechanism of apoptotic resistance. The presence of a hyperactive PARP1 mutation in one tumor was consistent with such increased NF-B activity. PARP1 inhibition restored p53-dependent apoptosis after IR in these leukemias by reducing NF-B DNA binding and transcriptional activity. In the remaining 4 ALL tumors, apoptotic resistance was associated with a TP53 mutation or with defective activation of p53. We conclude that increased NF-B prosurvival signaling is a frequent mechanism by which B-precursor ALL tumors develop apoptotic resistance to IR and that PARP1 inhibition may improve the DNA damage response of these leuke-

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Section: Discussionmentioning

confidence: 87%

Apoptotic resistance to ionizing radiation in pediatric B-precursor acute lymphoblastic leukemia frequently involves increased NF-κB survival pathway signaling

Weston

Austen

Wei

et al. 2004

Blood

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“…Constitutive upregulation of NF-kB has recently been correlated with progression of breast cancer, melanoma, and juvenile myelomonocytic leukemia (Kochetkova et al, 1997;Nakshatri et al, 1997;Raziuddin et al, 1997;Izban et al, 2000). How NF-kB is constitutively up-regulated in some tumor cells and what role it plays in acquiring resistance to apoptosis is not clear.…”

Section: Introductionmentioning

confidence: 99%

“…AraC potentiates cis-platin-, etoposide-, or taxolmediated cytotoxicity in SA-LPS/Jkt and HuT-78 cells NF-kB is known as an antiapoptotic factor (Kochetkova et al, 1997;Nakshatri et al, 1997;Raziuddin et al, 1997;Izban et al, 2000). In order to detect the role of NF-kB on cell viability, HuT-78 or SA-LPS/Jkt cells were incubated with 10 mm each of cis-platin, vincristine, doxorubicin, etoposide, adriamycin, or taxol and 50 mm of araC for 72 h and MTTassayed.…”

Section: Arac Induces Protein Phosphatases 2a and 2b-a Which Dephospmentioning

confidence: 99%

Mechanism of cytosine arabinoside-mediated apoptosis: role of Rel A (p65) dephosphorylation

2003

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“…For example, upregulation of TRAF1 has consistently been reported in lymphoid malignancies (Zapata et al, 2000;Durkop et al, 1999;Izban et al, 2000), with increased expression of TRAF1 in Epstein-Barr virus-transformed lymphoid cells and Reed-Sternberg cells in Hodgkin's disease.…”

Section: Tissue Expression Of Traf Proteinsmentioning

confidence: 99%

Tumor necrosis factor receptor-associated factors (TRAFs)

2001

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Expression of the Tumor Necrosis Factor Receptor-Associated Factors (TRAFs) 1 and 2 is a Characteristic Feature of Hodgkin and Reed-Sternberg Cells

Cited by 28 publications

References 40 publications

Apoptotic resistance to ionizing radiation in pediatric B-precursor acute lymphoblastic leukemia frequently involves increased NF-κB survival pathway signaling

Apoptotic resistance to ionizing radiation in pediatric B-precursor acute lymphoblastic leukemia frequently involves increased NF-κB survival pathway signaling

Mechanism of cytosine arabinoside-mediated apoptosis: role of Rel A (p65) dephosphorylation

Tumor necrosis factor receptor-associated factors (TRAFs)

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