p300-mediated acetylation of the Rothmund-Thomson-syndrome gene product RECQL4 regulates its subcellular localization

TY - JOUR

T1 - p300-mediated acetylation of the Rothmund-Thomson-syndrome gene product RECQL4 regulates its subcellular localization

AU - Dietschy, Tobias

AU - Shevelev, Igor

AU - Pena Diaz, Javier

AU - Hühn, Daniela

AU - Kuenzle, Sandra

AU - Mak, Raymond

AU - Miah, Mohammad Fahad

AU - Hess, Daniel

AU - Fey, Monika

AU - Hottiger, Michael O

AU - Janscak, Pavel

AU - Stagljar, Igor

PY - 2009/4/15

Y1 - 2009/4/15

N2 - RECQL4 belongs to the conserved RecQ family of DNA helicases, members of which play important roles in the maintenance of genome stability in all organisms that have been examined. Although genetic alterations in the RECQL4 gene are reported to be associated with three autosomal recessive disorders (Rothmund-Thomson, RAPADILINO and Baller-Gerold syndromes), the molecular role of RECQL4 still remains poorly understood. Here, we show that RECQL4 specifically interacts with the histone acetyltransferase p300 (also known as p300 HAT), both in vivo and in vitro, and that p300 acetylates one or more of the lysine residues at positions 376, 380, 382, 385 and 386 of RECQL4. Furthermore, we report that these five lysine residues lie within a short motif of 30 amino acids that is essential for the nuclear localization of RECQL4. Remarkably, the acetylation of RECQL4 by p300 in vivo leads to a significant shift of a proportion of RECQL4 protein from the nucleus to the cytoplasm. This accumulation of the acetylated RECQL4 is a result of its inability to be imported into the nucleus. Our results provide the first evidence of a post-translational modification of the RECQL4 protein, and suggest that acetylation of RECQL4 by p300 regulates the trafficking of RECQL4 between the nucleus and the cytoplasm.

AB - RECQL4 belongs to the conserved RecQ family of DNA helicases, members of which play important roles in the maintenance of genome stability in all organisms that have been examined. Although genetic alterations in the RECQL4 gene are reported to be associated with three autosomal recessive disorders (Rothmund-Thomson, RAPADILINO and Baller-Gerold syndromes), the molecular role of RECQL4 still remains poorly understood. Here, we show that RECQL4 specifically interacts with the histone acetyltransferase p300 (also known as p300 HAT), both in vivo and in vitro, and that p300 acetylates one or more of the lysine residues at positions 376, 380, 382, 385 and 386 of RECQL4. Furthermore, we report that these five lysine residues lie within a short motif of 30 amino acids that is essential for the nuclear localization of RECQL4. Remarkably, the acetylation of RECQL4 by p300 in vivo leads to a significant shift of a proportion of RECQL4 protein from the nucleus to the cytoplasm. This accumulation of the acetylated RECQL4 is a result of its inability to be imported into the nucleus. Our results provide the first evidence of a post-translational modification of the RECQL4 protein, and suggest that acetylation of RECQL4 by p300 regulates the trafficking of RECQL4 between the nucleus and the cytoplasm.

KW - Acetylation

KW - Amino Acid Motifs

KW - Amino Acid Sequence

KW - Cell Nucleus

KW - Cytoplasm

KW - E1A-Associated p300 Protein

KW - HeLa Cells

KW - Humans

KW - Lysine

KW - Molecular Sequence Data

KW - Mutation

KW - Nuclear Localization Signals

KW - Protein Processing, Post-Translational

KW - Protein Transport

KW - RecQ Helicases

KW - Recombinant Fusion Proteins

KW - Transfection

U2 - 10.1242/jcs.037747

DO - 10.1242/jcs.037747

M3 - Journal article

C2 - 19299466

SN - 0021-9533

VL - 122

SP - 1258

EP - 1267

JO - Journal of Cell Science

JF - Journal of Cell Science

IS - Pt 8

ER -