Ubiquitination of Notch1 is regulated by MAML1-mediated p300 acetylation of Notch1

Popko-Scibor, Anita E.; Lindberg, Mikael; Hansson, Magnus L.; Holmlund, Teresa; Wallberg, Annika E.

doi:10.1016/j.bbrc.2011.11.030

Cited by 31 publications

(24 citation statements)

References 26 publications

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“…We also found that p300 acetylates the Notch1 ICD in cell culture assays and in vitro , and that regions located within the Notch C-terminus are essential for Notch acetylation. MAML1 and CSL, components of the Notch transcription complex, strongly enhance Notch acetylation and we suggested that MAML1 increases Notch acetylation by potentiating p300 autoacetylation [12]. p300 can also acetylate MAML1, although the effect of this posttranslational modification on the function of MAML1 is currently unknown.…”

Section: Introductionmentioning

confidence: 89%

MAML1 Acts Cooperatively with EGR1 to Activate EGR1-Regulated Promoters: Implications for Nephrogenesis and the Development of Renal Cancer

Hansson¹,

Behmer²,

Ceder³

et al. 2012

PLoS ONE

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Mastermind-like 1 (MAML1) is a transcriptional coregulator of activators in various signaling pathways, such as Notch, p53, myocyte enhancer factor 2C (MEF2C) and beta-catenin. In earlier studies, we demonstrated that MAML1 enhanced p300 acetyltransferase activity, which increased the acetylation of Notch by p300. In this study, we show that MAML1 strongly induced acetylation of the transcription factor early growth response-1 (EGR1) by p300, and increased EGR1 protein expression in embryonic kidney cells. EGR1 mRNA transcripts were also upregulated in the presence of MAML1. We show that MAML1 physically interacted with, and acted cooperatively with EGR1 to increase transcriptional activity of the EGR1 and p300 promoters, which both contain EGR1 binding sites. Bioinformatics assessment revealed a correlation between p300, EGR1 and MAML1 copy number and mRNA alterations in renal clear cell carcinoma and p300, EGR1 and MAML1 gene alterations were associated with increased overall survival. Our findings suggest MAML1 may be a component of the transcriptional networks which regulate EGR1 target genes during nephrogenesis and could also have implications for the development of renal cell carcinoma.

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Section: Introductionmentioning

confidence: 89%

MAML1 Acts Cooperatively with EGR1 to Activate EGR1-Regulated Promoters: Implications for Nephrogenesis and the Development of Renal Cancer

Hansson¹,

Behmer²,

Ceder³

et al. 2012

PLoS ONE

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“…123 Acetylation by p300 HAT stabilizes NICD, whereas phosphorylation by CDK8 induces NICD degradation. Protein acetylation is reversible, and is regulated by histone deacetylases (HDACs), NAD-dependent protein deacetylases and histone acetyltransferases.…”

Section: Inhibition Of Notch Signallingmentioning

confidence: 99%

NUMB inhibition of NOTCH signalling as a therapeutic target in prostate cancer

et al. 2014

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Prostate cancer is among the most prevalent life-threatening cancers diagnosed in the male population today. Various methods have been exploited in an attempt to treat this disease but these treatments, alongside preventative tactics, have been insufficient to control mortality rates and have usually resulted in detrimental adverse events. An opportunity to devise more-specific and potentially more-effective approaches for the eradication of prostate tumours can be found by targeting specific biological pathways. NUMB (protein numb homologue), a key regulator of cell fate, represents an attractive, actionable target in prostate cancer. NUMB participates in the observed deregulation of NOTCH (neurogenic locus notch homologue protein) signalling in prostate tumours, and the NUMB–NOTCH interaction regulates cell fate. NUMB has potential both as a target for control of prostate tumorigenesis and as a biomarker for identification of patients with prostate cancer who are likely to benefit from NOTCH inhibition.

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“…Acetylation controls the stability of N IC (Popko-Scibor et al, 2011; Palermo et al, 2012). The deacetylase Sirtuin 1(SIRT1) has been reported as a key regulator of the endothelial Notch signaling (Guarani et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Notch inhibitors for cancer treatment

Espinoza¹,

Miele²

2013

Pharmacology & Therapeutics

243

225

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Notch signaling is an evolutionarily conserved cell signaling pathway involved in cell fate during development, stem cell renewal and differentiation in postnatal tissues. Roles for Notch in carcinogenesis, in the biology of cancer stem cells and tumor angiogenesis have been reported. These features identify Notch as a potential therapeutic target in oncology. Based on the molecular structure of Notch receptor, Notch ligands and Notch activators, a set of Notch pathway inhibitors have been developed. Most of these inhibitors had shown anti-tumor effects in preclinical studies. At the same time, the combinatorial effect of these inhibitors with current chemotherapeutical drugs still under study in different clinical trials. In this review, we describe the basics of Notch signaling and the role of Notch in normal and cancer stem cells as a logic way to develop different Notch inhibitors and their current stage of progress for cancer patient’s treatment.

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Ubiquitination of Notch1 is regulated by MAML1-mediated p300 acetylation of Notch1

Cited by 31 publications

References 26 publications

MAML1 Acts Cooperatively with EGR1 to Activate EGR1-Regulated Promoters: Implications for Nephrogenesis and the Development of Renal Cancer

MAML1 Acts Cooperatively with EGR1 to Activate EGR1-Regulated Promoters: Implications for Nephrogenesis and the Development of Renal Cancer

NUMB inhibition of NOTCH signalling as a therapeutic target in prostate cancer

Notch inhibitors for cancer treatment

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