SIRT1 interacts with p73 and suppresses p73‐dependent transcriptional activity

Dai, Jin; Wang, Zhi Yan; Sun, Dao Chun; Lin, Ru Xian; Wang, Sheng Qi

doi:10.1002/jcp.20831

Cited by 124 publications

(100 citation statements)

References 35 publications

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“…In addition to p53, the related proteins p63 and p73 mediate cell growth and tumorigenesis by regulating target genes similar to those of p53, and p73 is deacetylated by SIRT1 (Dai et al, 2007). Mice overexpressing an isoform of p63, DNp63a, under the keratin 14 promoter for specific expression in the basal cells of the skin, also age prematurely (Sommer et al, 2006).…”

Section: Sirt1 Promotes Replicative Senescence During Prolonged Exposmentioning

confidence: 99%

Sirtuins: critical regulators at the crossroads between cancer and aging

2007

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Sirtuins (SIRTs 1À7), or class III histone deacetylases (HDACs), are protein deacetylases/ADP ribosyltransferases that target a wide range of cellular proteins in the nucleus, cytoplasm, and mitochondria for post-translational modification by acetylation (SIRT1, -2, -3 and -5) or ADP ribosylation (SIRT4 and -6). The orthologs of sirtuins in lower organisms play a critical role in regulating lifespan. As cancer is a disease of aging, we discuss the growing implications of the sirtuins in protecting against cancer development. Sirtuins regulate the cellular responses to stress and ensure that damaged DNA is not propagated and that mutations do not accumulate. SIRT1 also promotes replicative senescence under conditions of chronic stress. By participating in the stress response to genomic insults, sirtuins are thought to protect against cancer, but they are also emerging as direct participants in the growth of some cancers. Here, we review the growing implications of sirtuins both in cancer prevention and as specific and novel cancer therapeutic targets.

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Section: Sirt1 Promotes Replicative Senescence During Prolonged Exposmentioning

confidence: 99%

Sirtuins: critical regulators at the crossroads between cancer and aging

2007

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“…40 However, this contradiction might be solved by the recent identification of two additional acetylation sites in the core domain of p53 that affect its transcriptional activity: K164 (modified by p300/CBP and pCAF) and K120 (modified by Tip60). 79,80 Moreover, the evidence that deacetylases such as HDAC1/2 and SIRT1 can inhibit p53 and p73 transcriptional activity [81][82][83] keeps alive the debate on the importance of acetylation for p53-family proteins.…”

Section: And References Therein)mentioning

confidence: 99%

p53-family proteins and their regulators: hubs and spokes in tumor suppression

2010

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The tumor suppressor p53 is a central hub in a molecular network controlling cell proliferation and death in response to potentially oncogenic conditions, and a wide array of covalent modifications and protein interactions modulate the nuclear and cytoplasmic activities of p53. The p53 relatives, p73 and p63, are entangled in the same regulatory network, being subject at least in part to the same modifications and interactions that convey signals on p53, and actively contributing to the resulting cellular output. The emerging picture is that of an interconnected pathway, in which all p53-family proteins are involved in the response to oncogenic stress and physiological inputs. Therefore, common and specific interactors of p53-family proteins can have a wide effect on function and dysfunction of this pathway. Many years of research have uncovered an impressive number of p53-interacting proteins, but much less is known about protein interactions of p63 and p73. Yet, many interactors may be shared by multiple p53-family proteins, with similar or different effects. In this study we review shared interactors of p53-family proteins with the aim to encourage research into this field; this knowledge promises to unveil regulatory elements that could be targeted by a new generation of molecules, and allow more efficient use of currently available drugs for cancer treatment.

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“…In addition to its role in chromatin regulation through histone deacetylation (discussed below; Figure 3), SirT1 has additional roles as a sensor of the metabolic status of the cell. These functions depend largely on the deacetylation of non-histone proteins that can be divided into three groups: transcription related factors: p53, PGC1-a, PPRg, the FOXO family of factors, MyoD, nuclear factor-kB (NF-kB), Bcl6, TAF I 68, E2F1, p73 and others, chromatin-related enzymes: the HATs p300 and P300/CBP-associated factor (PCAF), the corepressors NcoR/SMRT, the DNA-dependent protein kinase subunit Ku80, with the third group being signaling factors like Smad7 (Luo et al, 2001;Muth et al, 2001;Vaziri et al, 2001;Fulco et al, 2003;Brunet et al, 2004;Cohen et al, 2004;Motta et al, 2004;Picard et al, 2004;Yeung et al, 2004;Bouras et al, 2005;Rodgers et al, 2005;Wang et al, 2006;Dai et al, 2007;Kume et al, 2007).…”

Section: Class III Functionsmentioning

confidence: 99%

NAD+-dependent deacetylation of H4 lysine 16 by class III HDACs

2007

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Histone deacetylases (HDACs) catalyse the removal of acetyl groups from the N-terminal tails of histones. All known HDACs can be categorized into one of four classes (I-IV). The class III HDAC or silencing information regulator 2 (Sir2) family exhibits characteristics consistent with a distinctive role in regulation of chromatin structure. Accumulating data suggest that these deacetylases acquired new roles as genomic complexity increased, including deacetylation of non-histone proteins and functional diversification in mammals. However, the intrinsic regulation of chromatin structure in species as diverse as yeast and humans, underscores the pressure to conserve core functions of class III HDACs, which are also known as Sirtuins. One of the key factors that might have contributed to this preservation is the intimate relationship between some members of this group of proteins (SirT1, SirT2 and SirT3) and deacetylation of a specific residue in histone H4, lysine 16 (H4K16). Evidence accumulated over the years has uncovered a unique role for H4K16 in chromatin structure throughout eukaryotes. Here, we review the recent findings about the functional relationship between H4K16 and the Sir2 class of deacetylases and how that relationship might impact aging and diseases including cancer and diabetes.

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SIRT1 interacts with p73 and suppresses p73‐dependent transcriptional activity

Cited by 124 publications

References 35 publications

Sirtuins: critical regulators at the crossroads between cancer and aging

Sirtuins: critical regulators at the crossroads between cancer and aging

p53-family proteins and their regulators: hubs and spokes in tumor suppression

NAD+-dependent deacetylation of H4 lysine 16 by class III HDACs

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