The c-MYC oncoprotein is a substrate of the acetyltransferases hGCN5/PCAF and TIP60

Area of Science:

• Molecular Biology
• Epigenetics
• Oncology

Background:

• The c-MYC oncoprotein is a transcription factor crucial for cellular processes.
• Its function is partly regulated by cofactor complexes including histone acetyltransferases.
• These enzymes, such as mammalian GCN5 (mGCN5)/PCAF and TIP60, acetylate histones and other transcription factors.

Purpose of the Study:

• To investigate if c-MYC is a direct substrate for mGCN5/PCAF and TIP60.
• To identify the specific acetylation sites on c-MYC induced by mGCN5.

Main Methods:

• In vivo acetylation assays using human cells.
• Purification of c-MYC from human cells.
• Nanoelectrospray tandem mass spectrometry for site mapping.

Main Results:

• Demonstrated that mGCN5/PCAF and TIP60 directly acetylate c-MYC in vivo.
• Mapped the major mGCN5-induced acetylation sites on c-MYC.
• Showed that acetylation by either enzyme dramatically increases c-MYC protein stability.

Conclusions:

• c-MYC is a direct substrate of mGCN5/PCAF and TIP60.
• Acetylation by these enzymes stabilizes c-MYC.
• This represents a conserved mechanism for regulating c-MYC function via degradation rate.