The conserved WRPW motif of Hes6 mediates proteasomal degradation.
Hes6 belongs to a subfamily of basic helix-loop-helix transcription factors that includes Drosophila Hairy and Enhancer of split genes. Like other members of the family, Hes6 features the WRPW motif which is consisted just of four amino acids at its C-terminus. Here, we show that WRPW motif deletion mutant protein is substantially stabilized in comparison to the full length protein and that the enhanced stability is due to its resistance to proteasomal degradation. The WRPW motif also appears to be sufficient for acceleration of proteolysis as its fusion to two heterologous proteins, the green fluorescent protein (GFP) of Aequoria victoria and Gal4 DNA binding domain of Saccharomyces cerevisiae, significantly destabilized the proteins. These findings demonstrate a novel function of this conserved motif as a degradation signal and raise the possibility of utilizing it for controlling the level of ectopically expressed gene products.
Kang
Seon Ah
SA
Division of Molecular Life Sciences and Center for Cell Signaling Research, Ewha Womans University, 11-1 Daehyun-dong, Seodaemun-gu, Seoul 120-750, Korea.
Seol
Jae Hong
JH
Kim
Jaesang
J
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D051792:Basic Helix-Loop-Helix Proteins; D001673:Biodegradation, Environmental; D002460:Cell Line; D017124:Conserved Sequence; D006367:HeLa Cells; D006801:Humans; D007668:Kidney / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
D051792:Basic Helix-Loop-Helix Proteins; D046988:Proteasome Endopeptidase Complex; D011994:Recombinant Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C411859:HES6 protein, human; C061553:ATP dependent 26S protease