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发信人: leohawk (leohawk), 信区: Biology
标 题: Re: journal club today--p53&hsecurin
发信站: The unknown SPACE (Mon Feb 10 22:57:17 2003) WWW-POST
This is a pretty cool paper,
1. The experiment they used to show securing binding of P53 affects ability of
P53 to bind DNA, I think it is a long shot to have that conclusion, there are
plenty of other alternative explanations. However, their in vivo experiments
are very convincing.
2. Can anyone tell me how many AA can phage display vectors successfully
express?
A recent paper by ES. Lander and TR. Golub in nature genetics (Jan 2003) “A
molecular signature of metastasis in primary solid tumors” indicate that
securing(encoded by PTTG1), is overexpressed in metastases and is one of the
“expression signature” they used to test primary tumor for ability for
metastases. Heaney et al also noted that increased expression of securing in
tumors with increased vascularity and local invasion (Lancet, 355, 716-719,
2000). It will be interesting to see if P53 was mutated in those tumors then.
Taken together, we are looking at a much more complicated picture on how
securin, a protein thought to involved only in choromsome segregation, are
involved in more complicated processes, and can act at the center of signal
transduction that link chromosome segregation to other cellular events.
Below is some material I wrote on function of securing related protein in
meiotic chromosome segregation(it’s quite a while ago, I could not recollect
it all):
“In mitosis, the loss of cohesion between homologous chromosomes is caused by
the proteolytic cleavage of Scc1 by a specialized endopeptidase called separin
(Esp1 in S. cerevisiae, Cut1 in S. pombe), or separase (Uhlmann, Lottspeich et
al. 1999). Interestingly, the recognition sites of Scc1 for separin also exist
in Rec8. It has been shown that cleavage of Rec8 by Separin is essential for
the disjunction of homologous chromosome during meiosis I (Fig 4) (Buonomo
2000). During much of the cell cycle, securin (Pds1) inhibits separin
activity, which prevents undesired cleavage of Rec8. Onset of anaphase causes
ubiquitination and degradation of securin, which leads to separin activation
(Buonomo 2000). The degradation of Rec8 is a two-step process, first, Rec8
along the chromosome arms is degraded, but the Rec8 near the centromere region
are protected till the onset of meiosis II. It is apparent that this
protection ensures the cohesion between sister chromatids. The mechanism to
retain Rec8 at the centromere region is unknown”
It is worth noting that securing is also involved in orienting homologous
chromosome during meiotic chromosome segregation.
【 在 columxia (心向往之) 的大作中提到: 】
: Nature Genetics Vol32, Oct,2002 p306P311
: Human securin interacts with p53 and modulates p53-mediated transcriptional
: activity and apoptosis.
:
: The first report show the relevance between human securin and p53.
: The gene PTTG1 is considered human securin gene which can inhibit
: sister-chromatid separation in vertebrates, thus may contribute to
cell-cycle
: and tumorigenesis. The authors used phage display to identify the
interaction
: between hPTTG1 and p53, and they carried out a series of functional
analysises.
: And they proposed that the oncongenic effects of hsecurin may result form
: modulation of p53 functions.
:
: It is quite funny that another paper on JBC Jan,2003 reported that DNA
damage-
: induced inhibtion of securin expression is mediated by p53. So it seems the
2
: genes are regulated in a feedback loop.
:
: It is not hard to read through this paper and see the profound point in this
: paper.If you still remember the article in our 1st journal club, you can see
: a trend on understanding metaphase-anaphase checkpoint by securin/separase/
: Anaphase promoting comples study.
:
: That is my understanding. Comments and opinions highly apprecitaed. Thank
you.
:
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※ 来源:．The unknown SPACE bbs.mit.edu．[FROM: 128.6.]
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