Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43146 (tumour suppressor)
 5,935 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The p53 tumour suppressor is a transcriptional factor whose activity is modulated by protein stability and post-translational modifications including acetylation. The mechanism by which acetylated p53 is maintained in vivo remains unclear. Here we show that the deacetylation of p53 is mediated by an histone deacetylase-1 (HDAC1)-containing complex. We have also purified a p53 target protein in the deacetylase complexes (designated PID; but identical to metastasis-associated protein 2 (MTA2)), which has been identified as a component of the NuRD complex. PID specifically interacts with p53 both in vitro and in vivo, and its expression reduces significantly the steady-state levels of acetylated p53. PID expression strongly represses p53-dependent transcriptional activation, and, notably, it modulates p53-mediated cell growth arrest and apoptosis. These results show that deacetylation and functional interactions by the PID/MTA2-associated NuRD complex may represent an important pathway to regulate p53 function.
 ...
PMID:Deacetylation of p53 modulates its effect on cell growth and apoptosis. 1109 47

The p53 tumour suppressor exerts anti-proliferative effects, including growth arrest, apoptosis and cell senescence, in response to various types of stress. However, p53 is a short-lived protein and its activity is maintained at low levels in normal cells. Numerous studies indicate that CBP/p300-mediated acetyl-transferase activity is critical for its role in both catalysing p53 acetylation and activating p53-mediated function during stress response. Interestingly, two additional regulators have also been identified in the p53 acetylation pathway. PID/MTA2 is a p53-interacting protein that induces p53 deacetylation by recruiting the HDAC1 complex. Subsequent work has also identified Sir2alpha, a NAD-dependent histone deacetylase that can attenuate p53 transcriptional activity through deacetylation. The prominence of deacetylase activity on p53 certainly raises the defining question of its physiological purpose. It is likely that deacetylation proxides a quick acting mechanism to stop p53 function once transcriptional activation of target genes is no longer needed. We present data indicating that both HDAC1 and Sir2alpha are critical for p53-dependent stress response. Furthermore, we also try to define the functional consequence of p53 acetylation at the molecular level. Finally, we propose a model regarding the differential roles of HDAC1 and Sir2alpha in the regulation of p53 function.
 ...
PMID:Dynamics of the p53 acetylation pathway. 1517 Dec 55