Acetylation control of the retinoblastoma tumour-suppressor protein

2001 ◽  
Vol 3 (7) ◽  
pp. 667-674 ◽  
Author(s):  
Ho Man Chan ◽  
Marija Krstic-Demonacos ◽  
Linda Smith ◽  
Constantinos Demonacos ◽  
Nicholas B. La Thangue
Keyword(s):  
Tumour Suppressor ◽  
Tumour Suppressor Protein ◽  
Retinoblastoma Tumour Suppressor

Choosing between growth arrest and apoptosis through the retinoblastoma tumour suppressor protein, Abl and p73

2001 ◽  
Vol 29 (6) ◽  
pp. 666-673 ◽  
Author(s):  
J. Y. J. Wang ◽  
S. W. Ki
Keyword(s):  
Growth Arrest ◽  
Genotoxic Stress ◽  
Current Data ◽  
Cell Cycle Checkpoint ◽  
Tumour Suppressor ◽  
Apoptosis Pathway ◽  
Abl Tyrosine Kinase ◽  
Tumour Suppressor Protein ◽  
G1 Cells ◽  
Retinoblastoma Tumour Suppressor

The choice between growth arrest and apoptosis is made during differentiation, leading to survival with permanent arrest (e.g. neurons), or to death (e.g. epithelium). Genotoxic stress can also cause growth arrest or apoptosis, in addition to the activation of cell cycle checkpoint pathways. The p53 tumour suppressor can simulate growth arrest and apoptosis in response to DNA damage. Thus, p53 alone is not sufficient to specify these two mutually exclusive fates in damaged cells. The retinoblastoma tumour suppressor protein (RB) is a necessary downstream effector in p53-mediated growth arrest. RB inhibits E2F and the nuclear c-Abl tyrosine kinase. Interestingly, E2F activates the transcription of p73 mRNA and c-Abl stabilizes the p73 protein and activates its pro-apoptotic function. Because of RB, the c-Abl/p73 apoptosis pathway is activated in S/G2 cells but not in G1 cells. Taken together, the current data suggests RB to be an important player in directing the choice between permanent arrest and apoptosis. The antagonism between RB and c-Abl/p73 may modulate the function of p53 to direct the choice between growth arrest and apoptosis in DNA damaged cells.

scholarly journals Structure studies on the retinoblastoma tumour suppressor protein and its role in the cell cycle

2002 ◽  
Vol 58 (s1) ◽  
pp. c223-c223
Author(s):  
B. Xiao ◽  
J. Spencer ◽  
A. Clements ◽  
N. Ali-Khan ◽  
S. Mittnacht ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Tumour Suppressor ◽  
Tumour Suppressor Protein ◽  
Retinoblastoma Tumour Suppressor

scholarly journals Tudor-domain protein PHF20L1 reads lysine methylated retinoblastoma tumour suppressor protein

2017 ◽  
Vol 24 (12) ◽  
pp. 2139-2149 ◽  
Author(s):  
Simon M Carr ◽  
Shonagh Munro ◽  
Cari A Sagum ◽  
Oleg Fedorov ◽  
Mark T Bedford ◽  
...  
Keyword(s):  
Tumour Suppressor ◽  
Tumour Suppressor Protein ◽  
Tudor Domain ◽  
Domain Protein ◽  
Retinoblastoma Tumour Suppressor

scholarly journals Deacetylation of the retinoblastoma tumour suppressor protein by SIRT1

2007 ◽  
Vol 407 (3) ◽  
pp. 451-460 ◽  
Author(s):  
Sharon Wong ◽  
Jason D. Weber
Keyword(s):  
Tumour Suppressor ◽  
Sirtuin 1 ◽  
Tumour Suppressor Protein ◽  
Lysine Residues ◽  
Sirt1 Inhibitor ◽  
Rb Phosphorylation ◽  
Retinoblastoma Tumour Suppressor ◽  
Interfering Rna

The activity of Rb (retinoblastoma protein) is regulated by phosphorylation and acetylation events. Active Rb is hypophosphorylated and acetylated on multiple residues. Inactivation of Rb involves concerted hyper-phosphorylation by cyclin–CDK (cyclin-dependent kinase) complexes combined with deacetylation of appropriate lysine residues within Rb. In the present study, using in vivo co-immunoprecipitation experiments, we identified mammalian SIRT1 (sirtuin 1) as a binding partner for Rb and its family members p107 and p130. Formation of Rb–SIRT1 complexes required the pocket domain of Rb. p300 catalysed the acetylation of Rb, and SIRT1 was a potent deacetylase for Rb. The ability of SIRT1 to catalyse the deacetylation of Rb was dependent on NAD and was inhibited by the SIRT1 inhibitor nicotinamide. Deacetylated lysine residues within Rb formed a domain similar to the SIRT1-targeted domain of the p53 tumour suppressor protein. Cultures of arrested cells, via contact inhibition or DNA damage, exhibited decreased Rb phosphorylation and increased Rb acetylation. Overexpression of SIRT1 in either confluent or etoposide-treated cells resulted in a significant reduction in Rb acetylation, which was restored with nicotinamide. Gene knockdown of SIRT1 by siRNA (short interfering RNA) produced an accumulation of acetylated Rb. This increase was augmented further when siRNA against SIRT1 was used in conjunction with nicotinamide. In conclusion, our results demonstrate that SIRT1 is an in vitro and in vivo deacetylase for the Rb tumour suppressor protein.

Evidence for the p53 tumour suppressor protein as a direct sensor of DNA damage

2001 ◽  
Vol 37 ◽  
pp. S156-S157
Author(s):  
R. Bristow ◽  
S. Al-Rashid ◽  
F. Jalali ◽  
L. Lilge
Keyword(s):  
Dna Damage ◽  
Tumour Suppressor ◽  
Tumour Suppressor Protein

scholarly journals Regulation and function of the interaction between the APC tumour suppressor protein and EB1

Oncogene ◽  
2000 ◽  
Vol 19 (15) ◽  
pp. 1950-1958 ◽  
Author(s):  
J M Askham ◽  
P Moncur ◽  
A F Markham ◽  
E E Morrison
Keyword(s):  
Tumour Suppressor ◽  
Tumour Suppressor Protein ◽  
And Function

The p53 Tumour Suppressor Protein

2000 ◽  
Vol 17 (1) ◽  
pp. 179-212 ◽  
Author(s):  
Emma S. Hickman ◽  
Kristian Helin
Keyword(s):  
Tumour Suppressor ◽  
Tumour Suppressor Protein
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