PRIMA-1 induces apoptosis by inhibiting JNK signaling but promoting the activation of Bax

Wang, Tao; Lee, Kyung‐Hee; Rehman, Abdur; Daoud, Sayed S.

doi:10.1016/j.bbrc.2006.11.006

Cited by 36 publications

(42 citation statements)

References 25 publications

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“…PRIMA-1 and its derivative PRIMA-1 MET (also called APR-246) can restore wild-type protein conformation to TP53*. This restores transcriptional activity of normal TP53 that senses DNA damage, leading to expression of PUMA, NOXA , and BAX in TP53 -mutated cancer cells [168,169]. PRIMA-1 compounds are converted intracellularly to the Michael acceptor methylene quinuclidinone, subsequently binding covalently to cysteines of TP53*.…”

Section: Current Therapies and Novel Approachesmentioning

confidence: 99%

Emerging therapeutic targets in myeloproliferative neoplasms and peripheral T-cell leukemia and lymphomas

Orlova

Wingelhofer

Neubauer

et al. 2017

Expert Opinion on Therapeutic Targets

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Introduction: Hematopoietic neoplasms are often driven by gain-of-function mutations of the JAK-STAT pathway together with mutations in chromatin remodeling and DNA damage control pathways. The interconnection between the JAK-STAT pathway, epigenetic regulation or DNA damage control is still poorly understood in cancer cell biology. Areas covered: Here, we focus on a broader description of mutational insights into myeloproliferative neoplasms and peripheral T-cell leukemia and lymphomas, since sequencing efforts have identified similar combinations of driver mutations in these diseases covering different lineages. We summarize how these pathways might be interconnected in normal or cancer cells, which have lost differentiation capacity and drive oncogene transcription. Expert opinion: Due to similarities in driver mutations including epigenetic enzymes, JAK-STAT pathway activation and mutated checkpoint control through TP53, we hypothesize that similar therapeutic approaches could be of benefit in these diseases. We give an overview of how driver mutations in these malignancies contribute to hematopoietic cancer initiation or progression, and how these pathways can be targeted with currently available tools.

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Section: Current Therapies and Novel Approachesmentioning

confidence: 99%

Emerging therapeutic targets in myeloproliferative neoplasms and peripheral T-cell leukemia and lymphomas

Orlova

Wingelhofer

Neubauer

et al. 2017

Expert Opinion on Therapeutic Targets

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show abstract

“…ER stress can trigger apoptosis through two main pathways, either through the mitochondrial pathway involving Bcl-2 family proteins (Li et al, 2006) or through JNK through its activation by the IRE-1 kinase (Urano et al, 2000). This may explain why earlier studies have shown PRIMA-1 MET induced apoptosis through Bax and the mitochondrial pathway (Chipuk et al, 2003;Wang et al, 2007;Shen et al, 2008) or the JNK pathway in a mutant p53-dependent manner (Li et al, 2005).…”

Section: Prima-1 Induces Er Stress-mediated Apoptosis Jmr Lambert Et Almentioning

confidence: 99%

Mutant p53 reactivation by PRIMA-1MET induces multiple signaling pathways converging on apoptosis

et al. 2009

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“…There is evidence that both PRIMA-1 and PRIMA-1 MET induce the expression of mediators of p53-dependent apoptosis such as Puma, Noxa, and Bax in cells with mutant p53 Wang et al 2007). In addition, these compounds increase wild-type p53's as well as the p53R273H mutant's ability to cause cell death independently of their transcription factor function.…”

Section: Inhibitors Of Mdmxmentioning

confidence: 99%

p53-based Cancer Therapy

Lane¹,

Cheok²,

Laı́n³

2010

Cold Spring Harbor Perspectives in Biology

217

187

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Inactivation of p53 functions is an almost universal feature of human cancer cells. This has spurred a tremendous effort to develop p53 based cancer therapies. Gene therapy using wild-type p53, delivered by adenovirus vectors, is now in widespread use in China. Other biologic approaches include the development of oncolytic viruses designed to replicate and kill only p53 defective cells and also the development of siRNA and antisense RNA's that activate p53 by inhibiting the function of the negative regulators Mdm2, MdmX, and HPV E6. The altered processing of p53 that occurs in tumor cells can elicit T-cell and B-cell responses to p53 that could be effective in eliminating cancer cells and p53 based vaccines are now in clinical trial. A number of small molecules that directly or indirectly activate the p53 response have also reached the clinic, of which the most advanced are the p53 mdm2 interaction inhibitors. Increased understanding of the p53 response is also allowing the development of powerful drug combinations that may increase the selectivity and safety of chemotherapy, by selective protection of normal cells and tissues.

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PRIMA-1 induces apoptosis by inhibiting JNK signaling but promoting the activation of Bax

Cited by 36 publications

References 25 publications

Emerging therapeutic targets in myeloproliferative neoplasms and peripheral T-cell leukemia and lymphomas

Emerging therapeutic targets in myeloproliferative neoplasms and peripheral T-cell leukemia and lymphomas

Mutant p53 reactivation by PRIMA-1MET induces multiple signaling pathways converging on apoptosis

p53-based Cancer Therapy

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