【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
Unfortunately the substrate of SIRT6 is unlikely to be acetylated lysine, I wounder what will it be.
s*s
10 楼
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
11 楼
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
12 楼
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
13 楼
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.