Phospho‐ΔNp63α regulates <i>AQP3, ALOX12B, CASP14</i> and <i>CLDN1</i> expression through transcription and microRNA modulation

Ratovitski, Edward A.

doi:10.1016/j.febslet.2013.09.023

Cited by 13 publications

(8 citation statements)

References 32 publications

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“…A previous report has demonstrated the presence of a p53 response element in the AQP3 promoter such that members of the p53 family, including also p63 and p73, can induce AQP3 expression (Gu et al, 2008, Ratovitski, 2013, Zheng and Chen, 2001). In addition, p53 is known to be acetylated, with this post-translational modification enhancing its transcriptional activity (Li et al, 2002, Luo et al, 2004).…”

Section: Resultsmentioning

confidence: 98%

Regulation of the Glycerol Transporter, Aquaporin-3, by Histone Deacetylase-3 and p53 in Keratinocytes

Choudhary

Olala

Kagha

et al. 2017

Journal of Investigative Dermatology

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Aquaporin- (AQP) 3, a water and glycerol channel, plays an important role in epidermal function, with studies showing its involvement in keratinocyte proliferation, differentiation, and migration and in epidermal wound healing and barrier repair. Increasing speculation about the use of histone deacetylase (HDAC) inhibitors to treat skin diseases led us to investigate HDAC's role in the regulation of AQP3. The broad-spectrum HDAC inhibitor suberoylanilide hydroxamic acid induced AQP3 mRNA and protein expression in a dose- and time-dependent manner in normal keratinocytes. The SAHA-induced increase in AQP3 levels resulted in enhanced [H]glycerol uptake in normal but not in AQP3-knockout keratinocytes, confirming that the expressed AQP3 was functional. Use of HDAC inhibitors with different specificities limited our exploration of the responsible HDAC member to HDAC1, HDAC2, or HDAC3. Cre-recombinase-mediated knockdown and overexpression of HDAC3 suggested a role for HDAC3 in suppressing AQP3 expression basally. Further investigation implicated p53 as a transcription factor involved in regulating HDAC inhibitor-induced AQP3 expression. Thus, our study supports the regulation of AQP3 expression by HDAC3 and p53. Because suberoylanilide hydroxamic acid is already approved to treat cutaneous T-cell lymphoma, it could potentially be used as a therapy for skin diseases like psoriasis, where AQP3 is abnormally expressed.

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Section: Resultsmentioning

confidence: 98%

Regulation of the Glycerol Transporter, Aquaporin-3, by Histone Deacetylase-3 and p53 in Keratinocytes

Choudhary

Olala

Kagha

et al. 2017

Journal of Investigative Dermatology

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“…ΔNp63 controls distinct transcriptional networks depending on the state of maturation of keratinocyte precursors, which in turn is dependent on a variety of extracellular stimuli. In proliferating keratinocytes of the basal layers ΔNp63 controls the expression of basal layer keratins ( K5, K14 ) and of molecules required for the formation of the epidermal barrier, such as Alox12 [71] and inhibit proliferation‐induced activation of cell cycle arrest genes by competing with p53 for the same responsive elements. In response to differentiation stimuli, ΔNp63 detaches from the promoter of cell cycle arrest genes (e.g.…”

Section: P63 a Developmental Transcription Factormentioning

confidence: 99%

TP63 and TP73 in cancer, an unresolved “family” puzzle of complexity, redundancy and hierarchy

et al. 2014

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a b s t r a c t TP53 belongs to a small gene family that includes, in mammals, two additional paralogs, TP63 and TP73. The p63 and p73 proteins are structurally and functionally similar to p53 and their activity as transcription factors is regulated by a wide repertoire of shared and unique post-translational modifications and interactions with regulatory cofactors. p63 and p73 have important functions in embryonic development and differentiation but are also involved in tumor suppression. The biology of p63 and p73 is complex since both TP63 and TP73 genes are transcribed into a variety of different isoforms that give rise to proteins with antagonistic properties, the TA-isoforms that act as tumorsuppressors and DN-isoforms that behave as proto-oncogenes. The p53 family as a whole behaves as a signaling ''network'' that integrates developmental, metabolic and stress signals to control cell metabolism, differentiation, longevity, proliferation and death. Despite the progress of our knowledge, the unresolved puzzle of complexity, redundancy and hierarchy in the p53 family continues to represent a formidable challenge.

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“…Accumulated evidence suggests that the phosphorylated-ΔNp63α (p-ΔNp63α) transcription factor is indispensable for activation and inhibition of the expression of specific genes [ 126 , 127 ]. As the expression of miRNAs is consistently maintained by RNA polymerase II and III transcriptional machinery, the regulatory role of p-ΔNp63α in the miRNA maturation process is highly evident [ 128 , 129 ]. Indeed, Huang Y et al demonstrated that p-ΔNp63α can transcriptionally regulate microRNA gene promoters, while total ΔNp63α levels and p-ΔNp63α levels are maintained by miRNAs [ 130 ].…”

Section: Introductionmentioning

confidence: 99%

The microRNA feedback regulation of p63 in cancer progression

Lin

Zhang

et al. 2015

Oncotarget

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The transcription factor p63 is a member of the p53 gene family that plays a complex role in cancer due to its involvement in epithelial differentiation, cell cycle arrest and apoptosis. MicroRNAs are a class of small, non-coding RNAs with an important regulatory role in various cellular processes, as well as in the development and progression of cancer. A number of microRNAs have been shown to function as transcriptional targets of p63. Conversely, microRNAs also can modulate the expression and activity of p63. However, the p63–microRNA regulatory circuit has not been addressed in depth so far. Here, computational genomic analysis was performed using miRtarBase, Targetscan, microRNA.ORG, DIANA-MICROT, RNA22-HSA and miRDB to analyze miRNA binding to the 3′UTR of p63. JASPAR (profile score threshold 80%) and TFSEARCH datasets were used to search transcriptional start sites for p53/p63 response elements. Remarkably, these data revealed 63 microRNAs that targeted p63. Furthermore, there were 39 microRNAs targeting p63 that were predicted to be regulated by p63. These analyses suggest a crosstalk between p63 and microRNAs. Here, we discuss the crosstalk between p63 and the microRNA network, and the role of their interactions in cancer.

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Phospho‐ΔNp63α regulates AQP3, ALOX12B, CASP14 and CLDN1 expression through transcription and microRNA modulation

Cited by 13 publications

References 32 publications

Regulation of the Glycerol Transporter, Aquaporin-3, by Histone Deacetylase-3 and p53 in Keratinocytes

Regulation of the Glycerol Transporter, Aquaporin-3, by Histone Deacetylase-3 and p53 in Keratinocytes

TP63 and TP73 in cancer, an unresolved “family” puzzle of complexity, redundancy and hierarchy

The microRNA feedback regulation of p63 in cancer progression

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