Loss of function of <i>def</i> selectively up-regulates Δ<i>113p53</i> expression to arrest expansion growth of digestive organs in zebrafish

Chen, Jun; Ruan, Hua; Ng, Sok Meng Evelyn; Gao, Chuan; Soo, Hui Meng; Wu, Wei; Zhang, Zhenhai; Wen, Zilong; Lane, David P.; Peng, Jinrong

doi:10.1101/gad.1366405

Cited by 170 publications

(267 citation statements)

References 52 publications

Supporting

Mentioning

251

Contrasting

Unclassified

Order By: Relevance

“…58 The authors determined that D113p53 expression is regulated by def (digestive-organ expansion factor) gene. A loss-of-function mutation in def confers hypoplastic digestive organs and selectively upregulates the expression of D113p53 but not p53, resulting in compromised organ growth in def mutant Zebrafish.…”

Section: Conservation Through Evolution Of the P53 Gene Structurementioning

confidence: 99%

“…This hypothesis is supported by two recent publications. The authors 58 report that a loss-offunction mutation in def gene in Zebrafish confers hypoplastic digestive organs and selectively upregulates the expression of D113p53 (homologue of human D133p53) but not p53. The increased expression of D113p53 selectively induces the expression of p53-target genes involved in cell cycle arrest but not in apoptosis, resulting in compromised organ growth in def mutant Zebrafish.…”

Section: Biological Activities Of P53 and Its Isoformsmentioning

confidence: 99%

See 1 more Smart Citation

p53/p63/p73 isoforms: an orchestra of isoforms to harmonise cell differentiation and response to stress

2006

View full text Add to dashboard Cite

Abstractp63, p73 and p53 compose a family of transcription factors involved in cell response to stress and development. p53 is the most frequently mutated gene in cancer (50%) and loss of p53 activity is considered to be ubiquitous to all cancers. Recent publications may have a profound impact on our understanding of p53 tumour suppressor activity. p63, p73 and p53 genes have a dual gene structure conserved in drosophila, zebrafish and man. They encode for multiple p63, p73 or p53 proteins containing different protein domains (isoforms) due to multiple splicing, alternative promoter and alternative initiation of translation. In this review, we describe the different isoforms of p63, p73, p53 and their roles in development and cancer. The changes in the interactions between p53, p63 and p73 isoforms are likely to be fundamental to our understanding in the transition between normal cell cycling and the onset of tumour formation. Cell Death and Differentiation (2006) Introduction p53 was discovered in 1979 as a protein interacting with the oncogenic T antigen from SV40 virus. 1-5 p53 protein is the product of a pivotal tumor-suppressor gene whose inactivation by mutation or interaction with viral or overexpressed cellular proteins occurs in almost all cancers. 6 The p53 protein integrates multiple cellular stress signals assessing cellular damages to trigger either cell-cycle arrest or programmed cell death (apoptosis). 7 These effects are predominantly due to p53's ability to bind DNA through p53-responsive element (p53RE) 8,9 and regulate the transcription of genes involved in these processes, such as p21 10 (cell cycle arrest), Puma 11 or Scotin 12 (apoptosis). Thereby, p53 prevents proliferation of genetically abnormal cells and thus cancer formation.Two p53-related genes, p63 and p73, were identified in 1997. 13,14 The high level of sequence similarity between p63, p73 and p53 proteins, particularly in the DNA binding domain, allows p63 and p73 to transactivate p53-responsive genes causing cell cycle arrest and apoptosis. Therefore, p63, p73 and p53 genes form a family of transcription factor. However, they are not functionally entirely redundant and the primary role of each p53 family member -as determined by transgenetic knockout mice -illustrates that each protein has its own unique functions.We recently published that the p53 gene family has a dual gene structure conserved from drosophila to man. 15 Like most of the genes in the human genome, 16 p53 gene family members express multiple mRNA variants due to multiple splicing and alternative promoters. Hence, p53 gene family members express different forms of p53 protein containing different domain of the protein (isoforms). In this review, we will summarise the different isoforms of p63, p73 and p53 expressed in human, mouse and drosophila. p63The mouse p63 gene is composed of 15 exons spanning over 208 000 bp (GenBank Accession Number: AF533892) on chromosome 16, while the human p63 gene is composed of 15 exons, spanning over 270 000 bp on chromosome 3q2...

show abstract

Section: Conservation Through Evolution Of the P53 Gene Structurementioning

confidence: 99%

Section: Biological Activities Of P53 and Its Isoformsmentioning

confidence: 99%

p53/p63/p73 isoforms: an orchestra of isoforms to harmonise cell differentiation and response to stress

2006

View full text Add to dashboard Cite

show abstract

“…Recently, one of these isoforms has been shown to have a distinct and critical function in the development of the gut of zebra fish. 44 There is now clearly more to learn.…”

Section: The Core Control Of P53mentioning

confidence: 99%

The P53 pathway: what questions remain to be explored?

2006

View full text Add to dashboard Cite

The p53 pathway is composed of hundreds of genes and their products that respond to a wide variety of stress signals. These responses to stress include apoptosis, cellular senescence or cell cycle arrest. In addition the p53-regulated genes produce proteins that communicate these stress signals to adjacent cells, prevent and repair damaged DNA and create feedback loops that enhance or attenuate p53 activity and communicate with other signal transduction pathways. Many questions remain to be explored in our understanding of how this network of genes plays a role in protection from cancers, therapy and integrating the homeostatic mechanisms of stress management and fidelity in a cell and organism. The goal of this chapter is to elucidate some of those questions and suggest new directions for this area of research.

show abstract

“…We conclude that even though p53 knockdown effectively minimizes the pleiotropic effects associated with Sbds knockdown, it is unable to rescue Sbds ATG MO-induced organogenesis phenotypes. 113p53 (human) is both a shortened isoform and target gene of full-length p53 (Chen et al, 2005;. Although full-length p53 is dispensable for normal development, work in the zebrafish mutant def (digestive organ expansion factor, or diexf) has demonstrated that 113p53 plays an important role in endoderm development.…”

Section: Loss Of P53 Does Not Rescue the Sbds Organogenesis Phenotypesmentioning

confidence: 99%

Ribosomal biogenesis genes play an essential and p53-independent role in zebrafish pancreas development

et al. 2012

View full text Add to dashboard Cite

SUMMARYMutations in the human Shwachman-Bodian-Diamond syndrome (SBDS) gene cause defective ribosome assembly and are associated with exocrine pancreatic insufficiency, chronic neutropenia and skeletal defects. However, the mechanism underlying these phenotypes remains unclear. Here we show that knockdown of the zebrafish sbds ortholog fully recapitulates the spectrum of developmental abnormalities observed in the human syndrome, and further implicate impaired proliferation of ptf1a-expressing pancreatic progenitor cells as the basis for the observed pancreatic phenotype. It is thought that diseases of ribosome assembly share a p53-dependent mechanism. However, loss of p53 did not rescue the developmental defects associated with loss of zebrafish sbds. To clarify the molecular mechanisms underlying the observed organogenesis defects, we performed transcriptional profiling to identify candidate downstream mediators of the sbds phenotype. Among transcripts displaying differential expression, functional group analysis revealed marked enrichment of genes related to ribosome biogenesis, rRNA processing and translational initiation. Among these, ribosomal protein L3 (rpl3) and pescadillo (pes) were selected for additional analysis. Similar to knockdown of sbds, knockdown or mutation of either rpl3 or pes resulted in impaired expansion of pancreatic progenitor cells. The pancreatic phenotypes observed in rpl3-and pes-deficient embryos were also independent of p53. Together, these data suggest novel p53-independent roles for ribosomal biogenesis genes in zebrafish pancreas development.

show abstract

Loss of function of def selectively up-regulates Δ113p53 expression to arrest expansion growth of digestive organs in zebrafish

Cited by 170 publications

References 52 publications

p53/p63/p73 isoforms: an orchestra of isoforms to harmonise cell differentiation and response to stress

p53/p63/p73 isoforms: an orchestra of isoforms to harmonise cell differentiation and response to stress

The P53 pathway: what questions remain to be explored?

Ribosomal biogenesis genes play an essential and p53-independent role in zebrafish pancreas development

Contact Info

Product

Resources

About