P*******e
发帖数: 27 | 1 Hot off the press. A combination of two hot areas: Sirtuins and cancer
metabolism. I guess only a big bull can pull it off.
http://www.ncbi.nlm.nih.gov/pubmed/23217706 | z*t
发帖数: 863 | 2 corresponding author是独立时间不长的PI
现在很多人还想waburg effect除了PKM2之外的机制，这篇文章就是一个例子
【在 P*******e 的大作中提到】
: Hot off the press. A combination of two hot areas: Sirtuins and cancer
: metabolism. I guess only a big bull can pull it off.
: http://www.ncbi.nlm.nih.gov/pubmed/23217706
| A******y
发帖数: 2041 | 3 Unfortunately the substrate of SIRT6 is unlikely to be acetylated lysine, I
wounder what will it be. | s*******s
发帖数: 132 | 4 Why? How do you know?
I
【在 A******y 的大作中提到】
: Unfortunately the substrate of SIRT6 is unlikely to be acetylated lysine, I
: wounder what will it be.
| A******y
发帖数: 2041 | 5 Google SIRT5 and succinate etc. SIRT6 although has been reported to be a
deacetylase, but I think it is BS (don't worry no paper will be retracted,
just like all the class IIa HDAC paper). The activity is too low or none.
I think class IIa, IV, HDAC6 domain 1, and SIRT4, 6, and 7 substrates are
either not acetyl group or require special activation and highly context
dependent.
N.M. here is the link: http://www.ncbi.nlm.nih.gov/pubmed/22076378
P.S. I'm one of the reviewers of the SIRT5 paper.
【在 s*******s 的大作中提到】
: Why? How do you know?
:
: I
| P*******e
发帖数: 27 | 6
SIRT5 is kind of special since it has tyr and Arg in the substrate site.
These residues can interact with the carboxylate of succinate. I am not sure
you can make such a generalization.
If SIRT6 works through regulation of transcription, probably it doesn't need
to be very active in terms of deacetylation. As long as H3K56Ac at the
promoter of target genes can be selectively deacetylated, the effect can be
amplified by the transcription process assuming the acetylation is slow.
【在 A******y 的大作中提到】
: Google SIRT5 and succinate etc. SIRT6 although has been reported to be a
: deacetylase, but I think it is BS (don't worry no paper will be retracted,
: just like all the class IIa HDAC paper). The activity is too low or none.
: I think class IIa, IV, HDAC6 domain 1, and SIRT4, 6, and 7 substrates are
: either not acetyl group or require special activation and highly context
: dependent.
: N.M. here is the link: http://www.ncbi.nlm.nih.gov/pubmed/22076378
: P.S. I'm one of the reviewers of the SIRT5 paper.
| A******y
发帖数: 2041 | 7 That's only if you still believe that SIRTs are deacetylase. Their
activities compare to HDACs (metal containing deacetylases) are at least ten
times lower and reversible. Could it be that acetylation is actually done
by HDAC and a SIRT just serve as an recognition motif. The same mistake has
been made for class IIa HDAC. Unfortunately I still see people repeating
the wrong information on their papers. As for specific residue differences,
two domain of HDAC6 has little differences in amino acid sequences.
However,we already have some data (published and un-published) on how they
have significant different substrate and inhibitor selectivity. In addition,
the acetylated lysine antibody that most lab uses is a horrible antibody.
How do you know it is not looking at something close to acetyl group but in
reality is not?
Btw, I have no doubt about the validity of the paper. I just think the story
is more complex.
sure
need
be
【在 P*******e 的大作中提到】
:
:
: SIRT5 is kind of special since it has tyr and Arg in the substrate site.
: These residues can interact with the carboxylate of succinate. I am not sure
: you can make such a generalization.
: If SIRT6 works through regulation of transcription, probably it doesn't need
: to be very active in terms of deacetylation. As long as H3K56Ac at the
: promoter of target genes can be selectively deacetylated, the effect can be
: amplified by the transcription process assuming the acetylation is slow.
|
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