Lysine-specific modifications of p53: a matter of life and death?

Marouco, Diana; Garabadgiu, A. V.; Melino, Gerry; Barlev, Nikolai A.

doi:10.18632/oncotarget.1436

Cited by 80 publications

(88 citation statements)

References 126 publications

(156 reference statements)

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“…1,2,24,25,43,44 NIAM was previously shown to induce p53 transcriptional activity and cell cycle arrest, although its mechanisms of action were undefined. 34 Here, we explored how NIAM activates p53.…”

Section: Discussionmentioning

confidence: 99%

“…While ubiquitylation plays a dominant role in p53 regulation, other post-translational modifications of p53, including acetylation, are also instrumental in controlling its activity. 2,[23][24][25] Tip60 (HIV-Tat1 interactive protein of 60 kDa), a MYST-family histone acetyltransferase, has particular relevance to ARF-Mdm2-p53 signaling. Tip60 is a potent activator of p53 required for its induction of apoptosis, autophagy, and cell cycle inhibition.…”

Section: Introductionmentioning

confidence: 99%

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Nuclear interactor of ARF and Mdm2 regulates multiple pathways to activate p53

Reed¹,

Hagen²,

Tompkins³

et al. 2014

Cell Cycle

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Nuclear interactor of ARF and Mdm2 regulates multiple pathways to activate p53

Reed¹,

Hagen²,

Tompkins³

et al. 2014

Cell Cycle

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“…It is a transcription factor that prevents the transformation of cells by triggering protective mechanisms such as cell-cycle arrest or apoptosis (2,3). Several factors cooperate to determine cell fates induced by p53 after stress, although not all of them are known (4).…”

Section: Introductionmentioning

confidence: 99%

BTK Modulates p53 Activity to Enhance Apoptotic and Senescent Responses

et al. 2016

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Abstractp53 is a tumor suppressor that prevents the emergence of transformed cells by inducing apoptosis or senescence, among other responses. Its functions are regulated tightly by posttranslational modifications. Here we show that Bruton's tyrosine kinase (BTK) is a novel modulator of p53. We found that BTK is induced in response to DNA damage and p53 activation. BTK induction leads to p53 phosphorylation, which constitutes a positive feedback loop that increases p53 protein levels and enhances the transactivation of its target genes in response to stress. Inhibiting BTK reduced both p53-dependent senescence and apoptosis. Further, BTK expression also upregulated DNA damage signals and apoptosis. We conclude that despite being involved in oncogenic signals in blood malignancies, BTK has antineoplastic properties in other contexts, such as the enhancement of p53's tumor suppressor responses. Along with evidence that BTK expression correlates with good prognosis in some epithelial tumors, our findings may encourage a reevaluation of the clinical uses of BTK inhibitors in cancer therapy.

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“…10 In recent years, MDM2 has been recognized as the critical protein to target for p53 stabilization.…”

mentioning

confidence: 99%

Discovery of Novel Isatin-Based p53 Inducers

Davidovich

Aksenova

Petrova

et al. 2015

ACS Med. Chem. Lett.

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A series of isatin Schiff base derivatives were identified during in silico screening of the small molecule library for novel activators of p53. The compounds selected based on molecular docking results were further validated by a high-content screening assay using U2OS human osteosarcoma cells with an integrated EGFP-expressing p53-dependent reporter. The hit compounds activated and stabilized p53, as shown by Western blotting, at higher rates than the well-known positive control Nutlin-3. Thus, the p53-activating compounds identified by this approach represent useful molecular probes for various cancer studies.KEYWORDS: in silico, isatin Mannich and Schiff bases, p53 activators, in vivo assay, protein−protein interactions, MDM2

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Lysine-specific modifications of p53: a matter of life and death?

Cited by 80 publications

References 126 publications

Nuclear interactor of ARF and Mdm2 regulates multiple pathways to activate p53

Nuclear interactor of ARF and Mdm2 regulates multiple pathways to activate p53

BTK Modulates p53 Activity to Enhance Apoptotic and Senescent Responses

Discovery of Novel Isatin-Based p53 Inducers

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