再賺個一篇
A new p38 MAP kinase-regulated transcriptional
coactivator that stimulates p53-dependent apoptosis
Abstract:
When cells feel the environmental stresses such as UV or cisplatin treatment,
they will go from cell-cycle arrest to apoptosis through specific signaling
pathways. Among them the p38 mitogen-activated pretein kinase (MAPK)
signaling pathway is one of the most important cell-fate decisions.
P38α is the most widely studied member of the p38 MAPKs in higher
eukaryotes.It’s always activated by the MAPK kinases MKK6,MKK3 and MKK4 by
phosphorylat- ion. The ability of p38α may function as a tumor suppressor,
which can positively regulate several tumor suppressor pathways and attenuate
oncogenic signals. The role of p38α is to regulate the tumor suppressor
protein p53 through phosphorylati- on of p53. When p53 has been activated, it
can lead to reversible cell-cycle arrest, an irreversible senescence-like
state or apoptosis.
When the author’s team have identified a protein of 18kDa, which named
p18Hamlet specifically interact with human p38α. They found that p18Hamlet
protein are regulated by p38 MAPK. And p38 MAPK activation by UV treatment
also correlated with Thr phosphorylation of p18Hamlet. Because this
phosphorylation will be significa- ntly reduced when the cells were
pretreated with the p38 MAPK inhibitor SB203580.
The protein so-called p18Hamlet will accumulate when a cell experiencing DNA
damaging. And then the phenomenon will activate p53-dependent gene promoters
such as NOXA and PUMA due to the C-terminal zinc-finger HIT domain of
p18Hamlet. At last it causes cell-cycle arrest or apoptpsis. Therefore, the
author finds a new cell-fate regulator named p18Hamlet , which contributes to
the implementation of p53-regulated cellular responses.
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