The DNA-binding and transcriptional activities of MAZ, a myc-associated zinc finger protein, are regulated by casein kinase II.
Myc-associated zinc finger protein (MAZ) is a transcription factor that contains proline-rich, alanine repeats and six C(2)H(2)-type zinc finger motifs, as well as five putative sites of phosphorylation by casein kinase II (CKII). Site-specific mutagenesis of MAZ revealed that the serine residue at position 480 was the major site of phosphorylation by CKII both in vitro and in vivo. Phosphorylation of MAZ by CKII at this serine residue was required for maximum binding of MAZ to the pyrimidine-rich DNA of the nuclease-hypersensitive element (NHE) in the 5'-end promoter region of the c-myc gene. Mutation of serine at position 480 to alanine eliminated the DNA-binding activity of MAZ to this element. Moreover, the mutated MAZ was unable to enhance the expression of luciferase encoded by a c-myc promoter/luciferase reporter gene in HeLa cells in the presence of CKII. These results suggest that phosphorylation of the serine residue at position 480 of MAZ by CKII can control the function of MAZ by altering its DNA-binding activity.
Tsutsui
H
H
Tsukuba Life Science Center, RIKEN (The Institute of Physical and Chemical Research), 3-1-1 Koyadai, Tsukuba, Ibaraki, 305-0074, Japan.
Geltinger
C
C
Murata
T
T
Itakura
K
K
Wada
T
T
Handa
H
H
Yokoyama
K K
KK
D019943:Amino Acid Substitution; D047390:Casein Kinase II; D002467:Cell Nucleus / Q000378:metabolism; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D016259:Genes, myc / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020218:Response Elements / Q000235:genetics; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D004268:DNA-Binding Proteins; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; C076035:c-MYC-associated zinc finger protein; D010768:Phosphoserine; D004247:DNA; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases