Modulation of mammalian life span by the short isoform of p53.

By B. Maier, Wendy Gluba, B. Bernier, Terry T. Turner, K. Mohammad, T. Guise, A. Sutherland, M. Thorner, H. Scrable. Genes & Development, 2004

622 citations recorded by the source corpus.

Overexpression of the short isoform of p53 (p44) has unexpectedly uncovered a role for p53 in the regulation of size and life span in the mouse. Hyperactivation of the insulin-like growth factor (IGF) signaling axis by p44 sets in motion a kinase cascade that clamps potentially unimpeded growth through p21Cip1. This suggests that pathways of gene activity known to regulate longevity in lower organisms are linked in mammals via p53 to mechanisms for controlling cell proliferation. Thus, appropriate expression of the short and long p53 isoforms might maintain a balance between tumor suppression and tissue regeneration, a major requisite for long mammalian life span.

Subfields: Aging, Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/7428c7f8c1d6dd247d1cbde7cd78fe63fbe0973c

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Citations in the corpus

Cellular senescence in cancer and aging. (2007, positive): “Mice genetically manipulated to express constitutively active mutant p53 have greater protection against tumor development than wild-type mice, while at the same time they show signs of premature aging (Maier et al., 2004; Tyner et al., 2002).”
DNA damage response and cellular senescence in tissues of aging mice (2009, background): “Genetic activation of p53 shortened mice lifespan despite suppression of tumour formation (Tyner et al., 2002; Maier et al., 2004), while a p21 knock-out rescued at least some accelerated aging phenotypes in telomerase (mTERC) knockout mice (Choudhury et al.”
Insulin-like growth factors and neoplasia (2004, background): “These examples provide an interesting contrast to mice with increased p53 activit”
FOXO transcription factors at the interface between longevity and tumor suppression (2005, background): “Similarly, the expression of p44, an N-terminally truncated form of p53, which also leads to the activation of endogenous p53, elicit accelerated aging in mice (Maier et al., 2004).”
The Senescence-Associated Secretory Phenotype: The Dark Side of Tumor Suppression (2010, background): “The p53 tumor suppressor can also promote aging (111, 112) and senescence (7, 11, 12) in mice (see Figure 3).”
Senescence-Associated Secretory Phenotypes Reveal Cell-Nonautonomous Functions of Oncogenic RAS and the p53 Tumor Suppressor (2008, neutral): “accelerates aging phenotypes [31,32].”
Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors. (2005, background): “Cells from these modified mice were more susceptible to both p53-mediated apoptosis (Tyner et al., 2002) and p53-mediated senescence (Maier et al., 2004).”
Four faces of cellular senescence (2011, positive): “DNA-SCARS include dysfunctional telomeres or telomere dysfunction–induced foci (TIF; d’Adda di Fagagna et al., 2003; Takai et al., 2003; Herbig et al., 2004; Kim et al., 2004). replication fork collapse (Bartkova et al., 2006; Di Micco et al., 2006; Mallette et al., 2007).”
Stems cells and the pathways to aging and cancer. (2008, background): “, 1992), whereas mice overexpressing a short isoform (Maier et al., 2004) or truncated activated form of p53 (Tyner et al.”
p53 in health and disease (2007, background): “The observation that even a slight constitutive hyper-activation of p53 results in an alarming premature-ageing phenotype in mic”
p53 isoforms can regulate p53 transcriptional activity. (2005, background): “Received June 3, 2005; revised version accepted July 20, 2005. p53 was discovered 25 years ago as a protein interacting with the oncogenic T antigen from SV40 virus (De Leo et al. 1979; Kress et al. 1979; Lane and Crawford 1979; Linzer and Levine 1979; Melero et al. 1979).”