Cell cycle inhibitor p21/ WAF1/ CIP1 as a cofactor of MITF expression in melanoma cells

Šestáková, Blanka; Ondrušová, Lubica; Vachtenheim, J

doi:10.1111/j.1755-148x.2010.00670.x

Cited by 28 publications

(23 citation statements)

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“…] see Dotto, 2000;Perkins, 2002;Chen et al, 2009). p21 has been described to act both as a repressor and as a coactivator of the expression of genes (Poole et al, 2004;Fritah et al, 2005;Sestáková et al, 2010). Thus, the transcription function of p21 could be conserved in its Arabidopsis homolog KRP5 and provide a molecular link between the onset of endoreduplication and cell growth or differentiation.…”

Section: Discussionmentioning

confidence: 99%

Multiple Functions of Kip-Related Protein5 Connect Endoreduplication and Cell Elongation

et al. 2013

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Despite considerable progress in our knowledge regarding the cell cycle inhibitor of the Kip-related protein (KRP) family in plants, less is known about the coordination of endoreduplication and cell differentiation. In animals, the role of cyclindependent kinase (CDK) inhibitors as multifunctional factors coordinating cell cycle regulation and cell differentiation is well documented and involves not only the inhibition of CDK/cyclin complexes but also other mechanisms, among them the regulation of transcription. Interestingly, several plant KRPs have a punctuated distribution in the nucleus, suggesting that they are associated with heterochromatin. Here, one of these chromatin-bound KRPs, KRP5, has been studied in Arabidopsis (Arabidopsis thaliana). KRP5 is expressed in endoreduplicating cells, and loss of KRP5 function decreases endoreduplication, indicating that KRP5 is a positive regulator of endoreduplication. This regulation relies on several mechanisms: in addition to its role in cyclin/CDK kinase inhibition previously described, chromatin immunoprecipitation sequencing data combined with transcript quantification provide evidence that KRP5 regulates the transcription of genes involved in cell wall organization. Furthermore, KRP5 overexpression increases chromocenter decondensation and endoreduplication in the Arabidopsis trithoraxrelated protein5 (atxr5) atxr6 double mutant, which is deficient for the deposition of heterochromatin marks. Hence, KRP5 could bind chromatin to coordinately control endoreduplication and chromatin structure and allow the expression of genes required for cell elongation.

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Section: Discussionmentioning

confidence: 99%

Multiple Functions of Kip-Related Protein5 Connect Endoreduplication and Cell Elongation

et al. 2013

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“…Multiple signalling pathways converge on the MITF-M specific promoter that harbours binding sites for PAX3, SOX10, CREB, FOXD3, LEF-1 and BRN2 among other transcription factors (Yokoyama & Fisher, 2011; Levy, Khaled & Fisher, 2006). Additionally, the MITF target gene CDKN1A/P21 has been shown to act as reciprocal transcriptional cofactor independently of its CDK inhibitor function, suggesting the existence of at least one positive feedback loop (Sestáková, Ondrusová & Vachtenheim, 2010). …”

Section: Introductionmentioning

confidence: 99%

Loss of CITED1, an MITF regulator, drives a phenotype switchin vitroand can predict clinical outcome in primary melanoma tumours

Howlin

Cirenajwis

Lettiero

et al. 2015

PeerJ

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CITED1 is a non-DNA binding transcriptional co-regulator whose expression can distinguish the ‘proliferative’ from ‘invasive’ signature in the phenotype-switching model of melanoma. We have found that, in addition to other ‘proliferative’ signature genes, CITED1 expression is repressed by TGFβ while the ‘invasive’ signature genes are upregulated. In agreement, CITED1 positively correlates with MITF expression and can discriminate the MITF-high/pigmentation tumour molecular subtype in a large cohort (120) of melanoma cell lines. Interestingly, CITED1 overexpression significantly suppressed MITF promoter activation, mRNA and protein expression levels while MITF was transiently upregulated following siRNA mediated CITED1 silencing. Conversely, MITF siRNA silencing resulted in CITED1 downregulation indicating a reciprocal relationship. Whole genome expression analysis identified a phenotype shift induced by CITED1 silencing and driven mainly by expression of MITF and a cohort of MITF target genes that were significantly altered. Concomitantly, we found changes in the cell-cycle profile that manifest as transient G1 accumulation, increased expression of CDKN1A and a reduction in cell viability. Additionally, we could predict survival outcome by classifying primary melanoma tumours using our in vitro derived ‘CITED1-silenced’ gene expression signature. We hypothesize that CITED1 acts a regulator of MITF, functioning to maintain MITF levels in a range compatible with tumourigenesis.

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“…In this way, this study also developed a predictor model for survival identifying a group of patients with shorter overall survival associated with VGP melanoma, which was related to the absence of p16 INK4a or the presence of BCL6 protein expression in conjunction with either high Ki-67 expression or positive p21 CIP1 [22]. Although apparently paradoxical because of its cyclin-dependent inhibitory and tumor suppressor activities, a recent study reported that p21 CIP1 may also act as a tumor promoting factor by inhibiting apoptosis [23]. …”

Section: The Key Role Of Biomarkers In Melanoma Classification Refmentioning

confidence: 99%

Biomarkers as Key Contributors in Treating Malignant Melanoma Metastases

Souza

Morais

Jasiulionis

2012

Dermatology Research and Practice

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Melanoma is a human neurocristopathy associated with developmental defects in the neural crest-derived epidermal melanocytes. At the present time, at least three hypotheses were identified that may explain melanoma aetiology, as follows: (1) a model of linear progression from differentiated melanocytes to metastatic cancer cells (2) a model involving the appearance of melanoma stem-like cells, and (3) an epigenetic progenitor model of cancer. Treating metastatic melanoma is one of the most serious challenges in the 21st century. This is justified because of a subpopulation of cells presenting a remarkable molecular heterogeneity, which is able to explain the drug resistance and the growing mortality rates worldwide. Fortunately, there are now evidences sustaining the importance of genetic, epigenetic, and metabolomic alterations as biomarkers for classification, staging, and better management of melanoma patients. To illustrate some fascinating insights in this field, the genes BRAF V600E and CTLA4 have been recognized as bona fide targets to benefit melanoma patients. Our research attempts to carefully evaluate data from the literature in order to highlight the link between a molecular disease model and the key contribution of biomarkers in treating malignant melanoma metastases.

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Cell cycle inhibitor p21/ WAF1/ CIP1 as a cofactor of MITF expression in melanoma cells

Cited by 28 publications

References 50 publications

Multiple Functions of Kip-Related Protein5 Connect Endoreduplication and Cell Elongation

Multiple Functions of Kip-Related Protein5 Connect Endoreduplication and Cell Elongation

Loss of CITED1, an MITF regulator, drives a phenotype switchin vitroand can predict clinical outcome in primary melanoma tumours

Biomarkers as Key Contributors in Treating Malignant Melanoma Metastases

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