Alternative splicing of the p53 tumor suppressor gene in the Molt-4 T-lymphoblastic leukemia cell line

Chow, Vincent T.K.; Quek, Hung Hiang; Tock, E. P. C.

doi:10.1016/0304-3835(93)90256-9

Cited by 52 publications

(35 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Sugimoto et al, 1992) were examined. In addition, Molt-3 (lymphoblastoid T-cell leukaemia, unknown p53 status) and Molt-4 cells (lymphoblastoid Tcell leukaemia, originally derived from the same patient as Molt-3, and containing a splice site mutation in one p53 gene causing an in-frame stop codon, see Chow et al, 1993) were similarly studied. Apoptosis was induced using camptothecin or okadaic acid, 28S rRNA cleavage was analyzed after oligonucleotide hybridizations to Northern blots, and DNA fragmentation was analyzed on conventional 1% agarose gels (Figure 2).…”

Section: Resultsmentioning

confidence: 99%

The ability to cleave 28S ribosomal RNA during apoptosis is a cell-type dependent trait unrelated to DNA fragmentation

et al. 1997

View full text Add to dashboard Cite

Discrete cleavages within 28S rRNA divergent domains have previously been found to coincide with DNA fragmentation during apoptosis. Here we show that rRNA and DNA cleavages can occur independently in apoptotic cells, i.e. that the previously observed correlation is likely to be coincidental. In HL-60 cells, apoptosis with massive DNA fragmentation could be induced without any signs of rRNA cleavage. The opposite situation; rRNA cleavage without concomitant internucleosomal DNA fragmentation, was found in okadaic acid-treated Molt-4 cells. Other leukemia cell lines underwent apoptosis either without (K562 and Molt-3) or with (U937) both forms of polynucleotide cleavage. In K562 cells transfected with a temperature-sensitive p53 mutant, internucleosomal DNA fragmentation but not 28S rRNA cleavage was inducible by wild-type p53 expression. The absence of apoptotic rRNA cleavage in some cell types suggests that this phenomenon is tightly regulated and unrelated to DNA fragmentation or a presumed scheme for general macromolecular degradation in apoptotic cells.

show abstract

Section: Resultsmentioning

confidence: 99%

The ability to cleave 28S ribosomal RNA during apoptosis is a cell-type dependent trait unrelated to DNA fragmentation

et al. 1997

View full text Add to dashboard Cite

show abstract

“…Until recently, the p53 gene structure was much simpler. Only one promoter and three mRNA splice variants were described for p53, which would encode respectively full-length p53 (FLp53), p53i9 49,50 and D40p53. 51,52 The variant p53i9 is encoded by alternative splicing of the intron 9, a p53 protein isoform truncated of the last 60 amino acids of p53, defective in transcriptional activity.…”

Section: P53mentioning

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

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

“…However, other gene mutations or alterations in the cerh Afi hormone-binding domain cannot completely be excluded, e.g. exon deletion variants due to intronic splice site mutations which have frequently been found in the p53 gene in various cancers (28). Although the DNA-binding domain of the c-erbAP gene was not investigated, this region could be a possible target for mutations.…”

mentioning

confidence: 99%

The C-ErbAβ Thyroid Hormone Receptor Expression and cDNA sequence analysis of the hormone-binding domain in human cancer cell lines

Chow¹,

Lim²,

Tock³

1994

Acta Oncologica

View full text Add to dashboard Cite

Alternative splicing of the p53 tumor suppressor gene in the Molt-4 T-lymphoblastic leukemia cell line

Cited by 52 publications

References 23 publications

The ability to cleave 28S ribosomal RNA during apoptosis is a cell-type dependent trait unrelated to DNA fragmentation

The ability to cleave 28S ribosomal RNA during apoptosis is a cell-type dependent trait unrelated to DNA fragmentation

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

The C-ErbAβ Thyroid Hormone Receptor Expression and cDNA sequence analysis of the hormone-binding domain in human cancer cell lines

Contact Info

Product

Resources

About