Methods for identifying agents which alter histone protein acetylation, decrease aging or increase lifespan
AssigneeMassachusetts Institute of Technology
InventorsLEONARD GUARENTE, SHIN-ICHIRO IMAI, CHRISTOPHER ARMSTRONG
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Abstract
Methods of identifying agents which alter the NAD-dependent acetylation status and mono-ADP-ribosylation of nuclear proteins are disclosed. The methods further include identifying agents which alter the life span or aging of a cell or an organism by determining the level of NAD-dependent acetylation and/or ADP ribosylation of a nuclear protein. The invention also relates to a mammalian Sir2 protein which acetylates or deacetylates nuclear proteins in a NAD-dependent manner and has mono-ADP-ribosyltransferase activity. Host cells producing the Sir2 protein and antibodies to the Sir2 protein are also provided.
Claims15
A method of altering the NAD-dependent acetylation status of at least one amino acid residue in a protein the method comprising altering the activity of a Sir2 protein.
-27. (canceled)
A method of identifying an agent which alters mono-ADP-ribosylation of a nuclear protein in a cell, comprising the steps of:
- a) combining a cell and an agent to be tested;
- b) determining a level of mono-ADP-ribosylation of a nuclear protein in said cell;
- and
- c) comparing the level determined in step (b) with a level of mono-ADP-ribosylation of the nuclear protein in the absence of the agent to be tested,
- wherein a difference in the level of mono-ADP-ribosylation of the nuclear protein between the presence of the agent and the absence of the agent indicates that the agent alters mono-ADP-ribosylation of the nuclear protein.
-31. (canceled)
A method of identifying an agent which alters life span of a cell, comprising the steps of:
- a) combining a cell and an agent to be tested;
- b) determining a level of mono-ADP-ribosylation of a nuclear protein in said cell;
- and
- c) comparing the level determined in step (b) with a level of mono-ADP-ribosylation of the nuclear protein in the absence of the agent to be tested,
- wherein a difference in the level of mono-ADP-ribosylation of the nuclear protein between the presence of the agent and the absence of the agent indicates that the agent alters the life span of the cell.
-61. (canceled)
Dependencies are inferred from the claim text.