Emily Gillett

Bio: Emily Gillett is an academic researcher from Harvard University. The author has contributed to research in topics: Gene & Transactivation. The author has an hindex of 1, co-authored 1 publications receiving 2031 citations.

p63 is essential for regenerative proliferation in limb, craniofacial and epithelial development

Abstract: The p63 gene, a homologue of the tumour-suppressor p53, is highly expressed in the basal or progenitor layers of many epithelial tissues. Here we report that mice homozygous for a disrupted p63 gene have major defects in their limb, craniofacial and epithelial development. p63 is expressed in the ectodermal surfaces of the limb buds, branchial arches and epidermal appendages, which are all sites of reciprocal signalling that direct morphogenetic patterning of the underlying mesoderm. The limb truncations are due to a failure to maintain the apical ectodermal ridge, a stratified epithelium, essential for limb development. The embryonic epidermis of p63-/- mice undergoes an unusual process of non-regenerative differentiation, culminating in a striking absence of all squamous epithelia and their derivatives, including mammary, lacrymal and salivary glands. Taken together, our results indicate that p63 is critical for maintaining the progenitor-cell populations that are necessary to sustain epithelial development and morphogenesis.

p63 is a p53 homologue required for limb and epidermal morphogenesis.

Abstract: The p53 tumour suppressor is a transcription factor that regulates the progression of the cell through its cycle and cell death (apoptosis) in response to environmental stimuli such as DNA damage and hypoxia1,2. Even though p53 modulates these critical cellular processes, mice that lack p53 are developmentally normal3, suggesting that p53-related proteins might compensate for the functions of p53 during embryogenesis. Two p53 homologues, p63 and p73, are known4,5 and here we describe the function of p63 in vivo. Mice lacking p63 are born alive but have striking developmental defects. Their limbs are absent or truncated, defects that are caused by a failure of the apical ectodermal ridge to differentiate. The skin of p63-deficient mice does not progress past an early developmental stage: it lacks stratification and does not express differentiation markers. Structures dependent upon epidermal–mesenchymal interactions during embryonic development, such as hair follicles, teeth and mammary glands, are absent in p63-deficient mice. Thus, in contrast to p53, p63 is essential for several aspects of ectodermal differentiation during embryogenesis.

The first 30 years of p53: growing ever more complex

Abstract: When p53 was first discovered, it received relatively little attention from cancer researchers The road leading to p53's rise to fame, and the recognition ofTP53as the most frequently altered gene in human cancer, has been long and winding This Timeline examines the rich history of this pivotal tumour suppressor Thirty years ago p53 was discovered as a cellular partner of simian virus 40 large T-antigen, the oncoprotein of this tumour virus The first decade of p53 research saw the cloning of p53 DNA and the realization that p53 is not an oncogene but a tumour suppressor that is very frequently mutated in human cancer In the second decade of research, the function of p53 was uncovered: it is a transcription factor induced by stress, which can promote cell cycle arrest, apoptosis and senescence In the third decade after its discovery new functions of this protein were revealed, including the regulation of metabolic pathways and cytokines that are required for embryo implantation The fourth decade of research may see new p53-based drugs to treat cancer What is next is anybody's guess

The p53 pathway

Abstract: Abnormalities of the p53 tumour suppressor gene are among the most frequent molecular events in human and animal neoplasia. Moreover, p53 is one of the most studied proteins in the whole of contemporary biology, with more than 12,500 papers so far written! In this review the choice has been deliberately made not to be fully comprehensive in the coverage of the huge p53 literature. Rather attention is focused on a small number of recent developments which are reviewed in the context of modern models of p53 function. Progress in the analysis of signalling to p53 including phosphorylation cascades, and interactions with proteins such as mdm2 and ARF are highlighted. The plethora of protein-protein interactions is discussed, as are the strategies for defining downstream targets of p53. Finally, the emerging biology of p53 homologues is considered. The need for bridging the gap between reductionist, biochemical and biophysical studies and biological and genetic analysis is emphasized. Only this will provide the needed framework for utilizing the information in clinical care.