Acetylation regulates transcription factor activity at multiple levels.
CREB-binding protein (CBP) possesses an intrinsic acetyltransferase activity capable of acetylating nucleosomal histones as well as several nonhistone proteins. Here, it is shown that CBP can acetylate hepatocyte nuclear factor-4 (HNF-4), a member of the nuclear hormone receptor family, at lysine residues within the nuclear localization sequence. CBP-mediated acetylation is crucial for the proper nuclear retention of HNF-4, which is otherwise transported out to the cytoplasm via the CRM1 pathway. Acetylation also increases HNF-4 DNA binding activity and its affinity of interaction with CBP itself and is required for target gene activation. The results show that acetylation is a key posttranslational modification that may affect several properties of a transcription factor critical for the execution of its biological functions.
Soutoglou
E
E
Institute of Molecular Biology and Biotechnology Foundation for Research and Technology Hellas, Herakleion Crete, Greece.
Katrakili
N
N
Talianidis
I
I
D016475:3T3 Cells; D000107:Acetylation; D000123:Acetyltransferases / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D019556:COS Cells; D050882:CREB-Binding Protein; D002451:Cell Compartmentation; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D005786:Gene Expression Regulation; D051557:Hepatocyte Nuclear Factor 4; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism*; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D015533:Transcriptional Activation
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; D051557:Hepatocyte Nuclear Factor 4; D009687:Nuclear Proteins; D010750:Phosphoproteins; C501970:Tcfl4 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D000123:Acetyltransferases; D050882:CREB-Binding Protein; C494364:Crebbp protein, mouse