p63 steps into the limelight: crucial roles in the suppression of tumorigenesis and metastasis

Su, Xiaohua; Chakravarti, Deepavali; Flores, Elsa R.

doi:10.1038/nrc3446

Cited by 126 publications

(170 citation statements)

References 95 publications

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“…The alternatively spliced isoforms differ in their ability to transactivate downstream target genes that induce biological activities, such as cell-cycle arrest and apoptosis (Yang et al 1998). Importantly, some of the isoforms share more structural similarity to p53 and have been found to transactivate the same target genes such as p21, bax, NOXA, PUMA, and Perp (Yang et al 1998;Su et al 2013). p53 has also been found to have multiple isoforms driven by two promoters with carboxy-terminal spliced isoforms (Bourdon et al 2005): p53, p53b, p53g, D133p53, D133p53b, and D133p53g (Fig.…”

Section: The P53 Family and Its Isoformsmentioning

confidence: 99%

“…These are known as a, b, d, 1, g, z ( Fig. 1) (Su et al 2013). The alternatively spliced isoforms differ in their ability to transactivate downstream target genes that induce biological activities, such as cell-cycle arrest and apoptosis (Yang et al 1998).…”

Section: The P53 Family and Its Isoformsmentioning

confidence: 99%

“…2) (for review, see Koster and Roop 2007;Vanbokhoven et al 2011;Botchkarev et al 2012;Su et al 2013). p63 induces in epidermal keratinocytes the expression of the genes encoding basal epidermal keratins 5/14, distinct cell adhesion molecules (P-cadherin, integrin-a3, Perp, dystonin, etc.…”

Section: The P53 Family and Its Isoformsmentioning

confidence: 99%

“…In particular, the structure and role for the p63 gene as a master regulator of the development and maintenance of the stratified epithelia as well as its involvement in the control of aging and tumor growth were shown (reviewed in Koster and Roop 2007;Crum and McKeon 2010;Melino 2011;Vanbokhoven et al 2011;Su et al 2013). Furthermore, the roles of the distinct p63 and p73 isoforms in the control of cell proliferation, differentiation, and apoptosis in the skin were dissected by using a number of genetically engineered mouse models and in vitro analyses.…”

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confidence: 99%

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p53/p63/p73 in the Epidermis in Health and Disease

Botchkarev

Flores

2014

Cold Spring Harbor Perspectives in Medicine

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Although p53 has long been known as the "guardian of the genome" with a role in tumor suppression in many tissues, the discovery of two p53 ancestral genes, p63 and p73, more than a decade ago has triggered a considerable amount of research into the role of these genes in skin development and diseases. In this review, we primarily focus on mechanisms of action of p53 and p63, which are the best-studied p53 family members in the skin. The existence of multiple isoforms and their roles as transcriptional activators and repressors are key to their function in multiple biological processes including the control of skin morphogenesis, regeneration, tumorigenesis, and response to chemotherapy. Last, we provide directions for further research on this family of genes in skin biology and pathology.

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Section: The P53 Family and Its Isoformsmentioning

confidence: 99%

Section: The P53 Family and Its Isoformsmentioning

confidence: 99%

Section: The P53 Family and Its Isoformsmentioning

confidence: 99%

mentioning

confidence: 99%

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p53/p63/p73 in the Epidermis in Health and Disease

Botchkarev

Flores

2014

Cold Spring Harbor Perspectives in Medicine

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“…The p63 isoforms can be placed into two groups: the transactivation domain isoforms (TAp63), which structurally resemble p53 and act as tumor suppressors; and the DN isoforms (DNp63), which bind to p53, TAp63, and TAp73 and inhibit their function, thus acting as oncogenes (22)(23)(24). Unlike DNp63, TAp63 is not expressed or is present at low levels in a variety of cancers (25,26).…”

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confidence: 99%

YAP Expression and Activity Are Suppressed by S100A7 via p65/NFκB-mediated Repression of ΔNp63

Kong

Shao

et al. 2017

Molecular Cancer Research

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In several squamous cell carcinoma (SCC) cells, it has been previously observed that induction of the S100 calcium-binding protein A7 (S100A7) is repressed by YAP via the Hippo pathway. This report now demonstrates that S100A7 also represses YAP expression and activity by DNp63 in cancer cells. Stable overexpression of S100A7 activates the NFkB pathway and inhibits the expression of DNp63. Caffeic acid phenethyl ester (CAPE), as a specific inhibitor of NFkB, counteracts the inhibitory effect of S100A7 on the expression of DNp63 and its target genes. Depletion of S100A7 significantly promotes DNp63 expression. These data indicate that S100A7 acts as a suppressor of DNp63. Mechanistic examination finds that DNp63 not only directly binds to the region of YAP promoter and induces its expression, but also inhibits the Hippo pathway and enhances YAP activity. Importantly, either the positive correlation between S100A7 and YAP phosphorylation at S127 or the negative correlation between S100A7 and DNp63 is also observed in skin SCC tissues. Chemosensitivity analysis reveals that S100A7 enhances cancer cells' resistance by inhibition of YAP expression and activity. These results demonstrate that S100A7 is an upstream modulator of the Hippo pathway and extend our understanding of S100A7 functions in cancer.Implications: S100A7 is a new upstream regulator of the Hippo signaling pathway and reduces chemosensitivity of SCC cells through inhibitions of YAP expression and activity.

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Genomic profiling reveals distinctive molecular relapse patterns in IDH1/2 wild‐type glioblastoma

Riehmer

Gietzelt

Beyer

et al. 2014

Genes Chromosomes & Cancer

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Molecular changes associated with the progression of glioblastoma after standard radiochemotherapy remain poorly understood. We compared genomic profiles of 27 paired primary and recurrent IDH1/2 wild-type glioblastomas by genome-wide array-based comparative genomic hybridization. By bioinformatic analysis, primary and recurrent tumor profiles were normalized and segmented, chromosomal gains and losses identified taking the tumor cell content into account, and difference profiles deduced. Seven of 27 (26%) pairs lacked DNA copy number differences between primary and recurrent tumors (equal pairs). The recurrent tumors in 9/27 (33%) pairs contained all chromosomal imbalances of the primary tumors plus additional ones, suggesting a sequential acquisition of and/or selection for aberrations during progression (sequential pairs). In 11/27 (41%) pairs, the profiles of primary and recurrent tumors were divergent, i.e., the recurrent tumors contained additional aberrations but had lost others, suggesting a polyclonal composition of the primary tumors and considerable clonal evolution (discrepant pairs). Losses on 9p21.3 harboring the CDKN2A/B locus were significantly more common in primary tumors from sequential and discrepant (nonequal) pairs. Nonequal pairs showed ten regions of recurrent genomic differences between primary and recurrent tumors harboring 46 candidate genes associated with tumor recurrence. In particular, copy numbers of genes encoding apoptosis regulators were frequently changed at progression. In summary, approximately 25% of IDH1/2 wild-type glioblastoma pairs have stable genomic imbalances. In contrast, approximately 75% of IDH1/2 wild-type glioblastomas undergo further genomic aberrations and alter their clonal composition upon recurrence impacting their genomic profile, a process possibly facilitated by 9p21.3 loss in the primary tumor. © 2014 Wiley Periodicals, Inc.

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p63 steps into the limelight: crucial roles in the suppression of tumorigenesis and metastasis

Cited by 126 publications

References 95 publications

p53/p63/p73 in the Epidermis in Health and Disease

p53/p63/p73 in the Epidermis in Health and Disease

YAP Expression and Activity Are Suppressed by S100A7 via p65/NFκB-mediated Repression of ΔNp63

Genomic profiling reveals distinctive molecular relapse patterns in IDH1/2 wild‐type glioblastoma

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