BIOCHEMISTRY - DR. JAKUBOWSKI
Last Updated: 03/30/16
Learning Goals/Objectives for Chapter 5D: After class and this reading, students will be able to
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Acetylation of histones is obviously an important method in the control
of gene transcription. A recent study by Choudhary et al investigated
the effect and prevalence of lysine acetylation in a range of other cellular
pathways. The study discovered over 3600 acetylation sites on 1750 different
proteins comprising the acetylome using high resolution mass spectrometery.
These regulate a wide variety of dissimilar cellular function and showed
acetylation as a prevalent form of post translational modification falling
in terms of its frequency between the phosphoproteome and the spectrum of
ubiquitinated proteins. It is a highly conserved process occurring in many
different cellular lines from prokaryotes to human beings, and being as
prevalent as phosphoproteins found in the evolutionary tree.
Acetylation eliminates the positive charge on lysine side chains in a
reversible process. It has already been established that acetylation of
lysine side chains was a key component of DNA damage repair as it modifies
histone protein tails found in the DNA. However, recently it has been shown
that acetylation�s effects extend to regulation of other cellular functions.
Most commonly acetylation plays a role in nearly all nuclear functions, but
it also plays a surprisingly big role in cytoplasmic functions. One of the
new cellular functions investigated was the involvement of acetylation in
regulating macromolecular complexes within the cell pertaining to functions
such as signal transduction, DNA damage repair, and the cell cycle. One
example protein included in the study is the 14-3-3 protein which binds
specifically to phosphoserine or phosphothreonine in phosphorylatedpeptides.
Four different lysines in the protein were mutated to glutamine in an
attempt to determine the effect of acetylation on the protein's binding.
Acetylation was found to regulate binding as the enzyme�s activity was
severely harmed by mutation. This has been seen in other cellular processes
where acetylation has lead to regulation of enzymatic activity. In
addition, the study discovered that there is important interaction between
phosphorylation and acetylation. This interaction or �cross talk� between
acetylation and other post translational modification methods in regulating
cellular activity has been observed in the protein p53 as well which plays
an important role in repairing damaged DNA.
These protein are increasingly becoming targets for drug design as a way to alter gene transcription.
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