Nucleolar disruption ensures nuclear accumulation of p21 upon DNA damage.
Traffic
; 11(6): 743-55, 2010 Jun.
Article
em En
| MEDLINE
| ID: mdl-20331843
ABSTRACT
p21(cip1) is a protein with a dual function in oncogenesis depending mainly on its intracellular localization tumor suppressor in the nucleus and oncogenic in the cytoplasm. After DNA damage, p21(cip1) increases and accumulates in the nucleus to ensure cell cycle arrest. We show here that the nuclear accumulation of p21(cip1) is not only a consequence of its increased levels but to a DNA damage cellular response, which is ataxia telangiectasia and Rad3 related (ATR)/ataxia telangiectasia mutated (ATM) and p53 independent. Furthermore, after DNA damage, p21(cip1) not only accumulates in the nucleoplasm but also in the disrupted nucleolus. Inside the nucleolus, it is found in spherical structures, which are not a protrusion of the nucleoplasm. The steady-state distribution of p21(cip1) in the nucleolus resulted from a highly dynamic equilibrium between nucleoplasmic and nucleolar p21(cip1) and correlated with the inhibition of p21(cip1) nuclear export. Most interestingly, inhibition of ribosomal export after expressing a dominant-negative mutant of nucleophosmin induced p21(cip1) accumulation in the nucleus and the nucleolus in the absence of DNA damage. This proved the existence of a nucleolar export route to the cytoplasm for p21(cip1) in control conditions that would be inhibited upon DNA damage leading to nuclear and nucleolar accumulation of p21(cip1).
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Dano ao DNA
/
Nucléolo Celular
/
Núcleo Celular
/
Inibidor de Quinase Dependente de Ciclina p21
Limite:
Humans
Idioma:
En
Revista:
Traffic
Assunto da revista:
FISIOLOGIA
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Espanha