JOURNAL ARTICLE

Acetylation of Smad2 by the co-activator p300 regulates activin and transforming growth factor beta response

Andrea W Tu, Kunxin Luo
Journal of Biological Chemistry 2007 July 20, 282 (29): 21187-96
17478422
Transforming growth factor beta (TGFbeta) signals primarily through the Smad proteins to regulate cell growth, differentiation, and extracellular matrix production. Post-translational modifications, such as phosphorylation, play an important role in the regulation of the Smad proteins. TGFbeta signaling results in the phosphorylation of Smad2 and Smad3 that then oligomerize with Smad4 and translocate into the nucleus to initiate transcription of TGFbeta target genes. The initiation of transcription is significantly enhanced by the direct interaction of the Smad complex with p300/CBP (CREB-binding protein), a co-activator with intrinsic acetyltransferase activity. However, how p300/CBP enhances transcription through this interaction is not entirely understood. In this report, we show that Smad2, but not the highly homologous Smad3, can be acetylated by p300/CBP in a ligand-dependent manner. At least three lysine residues, Lys(19), Lys(20), and Lys(39), are required for efficient acetylation of Smad2, as mutations altering these lysines abolished Smad2 acetylation in vivo. This acetylation event is required for the ability of Smad2 to mediate activin and TGFbeta signaling. Mutation of the three key lysine residues did not alter the stability of Smad2 or the ability of Smad2 to form a complex with Smad4 on promoter DNA, but it prevented nuclear accumulation of Smad2 and subsequent TGFbeta and activin responses. Thus, our studies reveal a novel mechanism of modulating Smad2 activity and localization through protein acetylation.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read
17478422
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"