Hes6 controls cell proliferation via interaction with cAMP-response element-binding protein-binding protein in the promyelocytic leukemia nuclear body.
Hes6 is a basic helix-loop-helix transcription factor that functions in the differentiation of pluripotent progenitor cells and during tumorigenesis. However, the molecular mechanism for its function is largely unknown. Here we show that Hes6 is a component of the promyelocytic leukemia nuclear body (PML-NB) complex in the nuclei and that Hes6 inhibits cell proliferation through induction of p21 cyclin-dependent kinase inhibitor. We further show that Hes6 directly interacts with CREB-binding protein (CBP), one of the key components of PML-NB, via its basic domain. This association is critical for p21 induction through multiple mechanisms, including chromatin remodeling and p53 acetylation. Taken together, these results suggest that the Hes6-CBP complex in PML-NB may influence the proliferation of cells via p53-dependent and -independent pathways.
Eun
Bokkee
B
College of Medicine, Brain Korea 21, Korea University, Seoul 136-705, Korea.
Lee
Yool
Y
Hong
Soontaek
S
Kim
Jaesang
J
Lee
Han-Woong
HW
Kim
Kyungjin
K
Sun
Woong
W
Kim
Hyun
H
D000107:Acetylation; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D050882:CREB-Binding Protein / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D042002:Chromatin Assembly and Disassembly / Q000502:physiology; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D000071156:Promyelocytic Leukemia Protein; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
D051792:Basic Helix-Loop-Helix Proteins; D050882:CREB-Binding Protein; D050759:Cyclin-Dependent Kinase Inhibitor p21; D046912:Multiprotein Complexes; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D012097:Repressor Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C411859:HES6 protein, human; C070576:PML protein, human; C494363:CREBBP protein, human