One, two, three—p53, p63, p73 and chemosensitivity

Müller, Martina; Schleithoff, E. Schulze; Stremmel, Wolfgang; Melino, Gerry; Krammer, Peter H.; Schilling, Tobias

doi:10.1016/j.drup.2007.01.001

Cited by 126 publications

(113 citation statements)

References 179 publications

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“…This is consistent with earlier studies indicating that p63 is required for p53-dependent apoptotic response (9) and that, in response to certain DNA damage insults, p63 activates an overlapping set of p53-target genes implicated in cell cycle arrest and apoptosis (10). Although extensive studies of p63 in human tumors have suggested that deregulated expression of TAp63 and ⌬Np63 contributes to tumor development and progression (4), the precise molecular mechanisms behind the transcriptional regulation of TAp63 remain to be unclear.…”

supporting

confidence: 78%

“…A representative example of such a factor is the tumor suppressor p53 and its family members, including p63 and p73, which contribute to tumor suppression, cell cycle checkpoint, DNA repair, and apoptosis (1). p63 acts as a pro-apoptotic transcription factor (2,3) and, like p53 and p73, is expressed as multiple isoforms (4). They include the trans-activating (TA) 3 isoform of p63, termed TAp63, and an NH 2 -terminal activation domain-deficient isoform, ⌬Np63, that acts as a dominant negative factor over p53, TAp63, and TAp73 (2).…”

mentioning

confidence: 99%

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TATA-binding Protein (TBP)-like Protein Is Engaged in Etoposide-induced Apoptosis through Transcriptional Activation of Human TAp63 Gene

Suenaga

Ozaki

Tanaka

et al. 2009

Journal of Biological Chemistry

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Accumulating evidence indicates that TBP (TATA-binding protein)-like protein (TLP) contributes to the regulation of stress-mediated cell cycle checkpoint and apoptotic pathways, although its physiological target genes have remained elusive. In the present study, we have demonstrated that human TAp63 is one of the direct transcriptional target genes of TLP. Enforced expression of TLP results in the transcriptional induction of the endogenous TAp63, but not of the other p53 family members such as TAp73 and p53. Consistent with these results, small interference RNA-mediated knockdown led to a significant down-regulation of the endogenous TAp63. Luciferase reporter assay and chromatin immunoprecipitation analysis revealed that the genomic region located at positions ؊487 to ؊29, where ؉1 represents the transcriptional initiation site of TAp63, is required for TLP-dependent transcriptional activation of TAp63 and also TLP is efficiently recruited onto this region. Additionally, cells treated with anti-cancer drug etoposide underwent apoptosis in association with the transcriptional enhancement of TAp63 in a p53-independent manner, and the knockdown of the endogenous TLP reduced etoposide-induced apoptosis through repression of TAp63 expression. Taken together, our present study identifies a TLP-TAp63 pathway that is further implicated in stress-induced apoptosis.Transcriptional regulation involves the functional integration of diverse factors and is a critical regulatory step for cellular events that include growth, differentiation, and death. These cellular activities often occur simultaneously due to the action of regulatory factors with broad targets. A representative example of such a factor is the tumor suppressor p53 and its family members, including p63 and p73, which contribute to tumor suppression, cell cycle checkpoint, DNA repair, and apoptosis (1). p63 acts as a pro-apoptotic transcription factor (2, 3) and, like p53 and p73, is expressed as multiple isoforms (4). They include the trans-activating (TA) 3 isoform of p63, termed TAp63, and an NH 2 -terminal activation domain-deficient isoform, ⌬Np63, that acts as a dominant negative factor over p53, TAp63, and TAp73 (2). p63 has been clearly implicated in a variety of developmental processes (5), whereas its anticipated role as a tumor suppressor is unclear, mainly because of its low frequency of the somatic mutations in human tumors (6, 7). However, a study focused on long term effects of p63 mutations in mice showed that mice bearing mutations in both p63 and p53 develop a more aggressive tumor, indicating the presence of a tumor suppressive activity of p63 (8). This is consistent with earlier studies indicating that p63 is required for p53-dependent apoptotic response (9) and that, in response to certain DNA damage insults, p63 activates an overlapping set of p53-target genes implicated in cell cycle arrest and apoptosis (10). Although extensive studies of p63 in human tumors have suggested that deregulated expression of TAp63 and ⌬Np63 contributes to tu...

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supporting

confidence: 78%

mentioning

confidence: 99%

TATA-binding Protein (TBP)-like Protein Is Engaged in Etoposide-induced Apoptosis through Transcriptional Activation of Human TAp63 Gene

Suenaga

Ozaki

Tanaka

et al. 2009

Journal of Biological Chemistry

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“…p53 forms a gene family including transactivating p63 (TAp63) and p73, all of which have the same consensus sequence (14). TAp63 has a role in differentiation as well as apoptosis induction and tumor suppression (15)(16)(17). We have found that TBP-like protein (TLP) enhances activity of the promoter of TAp63 gene, which induces apoptotic cell death, and we have presented a TLP-TAp63 pathway model to explain etoposide-triggered apoptosis (18).…”

Section: Waf1/cip1mentioning

confidence: 99%

TATA-binding Protein (TBP)-like Protein Is Required for p53-dependent Transcriptional Activation of Upstream Promoter of p21 Gene

Suzuki

Itô

Ikeda

et al. 2012

Journal of Biological Chemistry

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Background: TLP and p21 are involved in growth inhibition. Results: TLP decreased cell growth and activated upstream promoter of p21 gene p53-dependently. TLP bound to p53. The promoter was associated with TLP and p53, and TLP enhanced recruitment of p53 to the promoter. Conclusion: TLP is required for p53-dependent transcriptional activation of p21 upstream promoter. Significance: A novel regulator for p53-p21 pathway was identified.

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“…p53 is a member of a transcription factor family that also comprises p63 and p73. 115 Similar to p53, p63 and p73 are also activated by a broad range of DNA-damaging agents and induce apoptosis via the intrinsic death pathway through transactivation of almost an identical set of genes. However, they do not entirely act in a redundant fashion and each protein was shown to exhibit its own unique functions as determined in transgenic knockout mice.…”

Section: Dral (Downregulated In Rhabdomyosarcoma Lim Protein); Klf4 (mentioning

confidence: 99%

The dark side of a tumor suppressor: anti-apoptotic p53

2008

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Depending on multiple factors DNA damage leads either to cell cycle arrest or apoptosis. One of the main players deciding the fate of a cell is the tumor suppressor p53 that modulates these responses in a transcription-dependent and -independent manner. Over the past few years, however, strong evidence accumulated that p53 engages also powerful pro-survival pathways by transcriptionally activating a multitude of genes whose products efficiently counteract apoptosis. Our review summarizes the current knowledge concerning approximately forty p53-regulated proteins that exert their anti-apoptotic potential by interfering with diverse cellular processes. These activities are surely essential for normal development and maintenance of a healthy organism, but may easily turn into the dark side of the tumor suppressor p53 contributing to tumorigenesis.

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One, two, three—p53, p63, p73 and chemosensitivity

Cited by 126 publications

References 179 publications

TATA-binding Protein (TBP)-like Protein Is Engaged in Etoposide-induced Apoptosis through Transcriptional Activation of Human TAp63 Gene

TATA-binding Protein (TBP)-like Protein Is Engaged in Etoposide-induced Apoptosis through Transcriptional Activation of Human TAp63 Gene

TATA-binding Protein (TBP)-like Protein Is Required for p53-dependent Transcriptional Activation of Upstream Promoter of p21 Gene

The dark side of a tumor suppressor: anti-apoptotic p53

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