Structural Biochemistry/Enzyme/Acetyltransferase

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Acetyl group

An acetyltransferase is an enzyme that catalyzes the transfer of acetyl groups.

p300/CBP[edit]

p300 and CREB binding protein (CBP) are both acetyltransferases that are highly conserved. Both have specific domains within the enzyme: three cysteine-histidine rich domains, bromodomain, and acetyltransferase domain. CBP/p300 phosphorylation activates acetyltransferase activity, which increases histone acetylation at target promoters and facilitates CBP/p300-dependent transactivation of genes. The acetyltransferase domains in these enzymes also uncovered autoacetylation activity. Autoacetylation of these enzymes causes a conformational change of the histone as well as the enzyme itself that directly affects the enzyme's ability to interact with Mediator, which is a multi-protein complex that plays an important role in the beginning stages of transcriptional activation.

TIP60[edit]

TIP60 is party of the MYST family of acetyltransferases conserved from yeast to humans. It acetylates core histones H2A, H3, and H4. This enzyme plays a crucial role in DNA damage response and apoptosis. TIP60 acetylizes the ataxia telangiectasia mutated (ATM) kinase, which is the central kinase in the repair pathways started by DNA lesions. Studies also show that ATF2 interacts with TIP60 and modulates its function at the DNA damage response step. Before DNA damage, ATF2 has low TIP60 levels by facilitationg TIP60 degradation. After DNA damage, TIP60 and ATF2 are more loosely associated. In addition, the sumoylation of TIP60 plays a key role in the localization and catalytic activity of the enzyme, influencing the enzyme's ability to help with DNA damage. Through experiments and observations, researchers have concluded that there is an important link between TIP60 levels and the signals generated by DNA damage response pathways. Evidence shows that human prostate cancer samples display loss of TIP60 and human lymphomas and mammary tumors display loss of TIP60.

Reference[edit]

Mellert, Hestia S. and McMahon, Steven B. "Biochemical pathways that regulate acetyltransferase and deacetylase activity in mammalian cells." Trends in Biochemical Sciences Vol. 34 No. 11. 2009.