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Beclin 1, a protein essential for autophagy, regulates autophagy by interacting withVps34and other cofactors to form the Beclin 1 complex.Modifications of Beclin 1may lead to the induction, inhibition or fine-tuning of the autophagic response under a variety of conditions.Here we show that Beclin 1 is acetylated by p300 and deacetylated by SIRT1 at lysine residues 430 and 437.In addition, the phosphorylation of Beclin 1 at S409 by CK1 is required for the subsequent p300 binding and Beclin 1 acetylation. Beclin 1 acetylation inhibits autophagosome maturation and endocytic trafficking by promoting the recruitment of Rubicon. In rumor xenografts, the expression of 2KR mutant Beclin 1 (substitution of K430 and K437 to arginines)leads to enhanced autophagosome maturation and tumor growth suppression. Therefore, our study identifies an acetylation-dependent regulatory mechanism governing Beclin 1 function in autophagosome maturation and tumor growth.