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Titolo:
LOSS OF FUNCTION AND P53 PROTEIN STABILIZATION
Autore:
BLAGOSKLONNY MV;
Indirizzi:
NCI,MED BRANCH,NIH,BLDG 10 BETHESDA MD 20892
Titolo Testata:
Oncogene
fascicolo: 16, volume: 15, anno: 1997,
pagine: 1889 - 1893
SICI:
0950-9232(1997)15:16<1889:LOFAPP>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
TUMOR-SUPPRESSOR PROTEIN; CANCER CELL-LINES; MUTANT P53; SV40-TRANSFORMED CELLS; TRANSFORMED-CELLS; BREAST-CANCER; METABOLIC STABILIZATION; ACTIVATING MUTATIONS; DNA-BINDING; T-ANTIGEN;
Keywords:
P53; STABILIZATION; MUTANT; TRANSACTIVATING FUNCTION;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
67
Recensione:
Indirizzi per estratti:
Citazione:
M.V. Blagosklonny, "LOSS OF FUNCTION AND P53 PROTEIN STABILIZATION", Oncogene, 15(16), 1997, pp. 1889-1893

Abstract

Wild-type (wt) p53 protein is rapidly degraded, has a short half-lifeand low intracellular levels. Stabilization of wt p53 protein following an appropriate stimulus (for example DNA damage) is a physiologicalregulation to increase function. Tn contrast, stabilization of p53 protein in the absence of a stimulus is always a hallmark of loss of function secondary to a mutation, or interaction with viral or cellular oncoproteins. It is generally accepted that stability of p53 protein depends on its intrinsic biochemical properties such as conformation or protein/protein interactions. However, I will discuss evidence that the stability of p53 is not a consequence of its intrinsic properties, but instead is determined by feedback control of its function. In the absence of an appropriate stimulus, a cell needs to keep p53 levels low, since increased levels can lead to apoptosis. To precisely regulate p53 levels, a cell must sense its level; and sensing its transactivating function, is the simplest way to sense p53. Following an appropriate stimulus (for example, DIVA damage), the cell senses a state of 'relative' p53 deficiency and adapts by reducing p53 degradation. When thestate of p53 deficiency is a consequence of a mutation or interactionwith viral oncoproteins, the cell does not sense p53, and again attempts to adapt by reducing p53 degradation. However, in the latter case,the increase in levels does not restore function, and the adaptation continues until degradation of p53 protein is maximally inhibited. In this case, no further inhibition of degradation is possible after DNA-damage or pharmacological inhibition of proteasomes. Thus lack of wt p53 function always results in increased p53 levels and nonregulation.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/11/20 alle ore 15:32:28