title: Smurf2 regulates the degradation of YY1.
abstract: Transcription factor YY1 plays important roles in cell proliferation and differentiation. For example, YY1 represses the expression of muscle-specific genes and the degradation of YY1 is required for myocyte differentiation. The activity of YY1 can be regulated by various post-translational modifications; however, little is known about the regulatory mechanisms for YY1 degradation. In this report, we attempted to identify potential E3 ubiquitin ligases for YY1, and found that Smurf2 E3 ubiquitin ligase can negatively regulate YY1 protein level, but not mRNA level. Smurf2 interacted with YY1, induced the poly-ubiquitination of YY1 and shortened the half-life of YY1 protein. Conversely, an E3 ubiquitin ligase-defective mutant form of Smurf2 or knockdown of Smurf2 increased YY1 protein level. PPxY motif is a typical target recognition site for Smurf2, and the PPxY motif in YY1 was important for Smurf2 interaction and Smurf2-induced degradation of YY1 protein. In addition, Smurf2 reduced the YY1-mediated activation of a YY1-responsive reporter whereas Smurf2 knockdown increased it. Finally, Smurf2 relieved the suppression of p53 activity by YY1. Taken together, our results suggest a novel regulatory mechanism for YY1 function by Smurf2 in which the protein stability and transcriptional activity of YY1 are regulated by Smurf2 through the ubiquitin-proteasome-mediated degradation of YY1.
authors.affiliation: College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju 500-757, South Korea.
authors.forename: Hyung Min
authors.initials: HM
authors.lastname: Jeong
authors.affiliation: College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju 500-757, South Korea.
authors.forename: Sung Ho
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Life Science and Global Top5 Research Program, Ewha Womans University, Seoul 120-750, South Korea.
authors.forename: Jinah
authors.initials: J
authors.lastname: Yum
authors.affiliation: Department of Life Science and Global Top5 Research Program, Ewha Womans University, Seoul 120-750, South Korea.
authors.forename: Chang-Yeol
authors.initials: CY
authors.lastname: Yeo
authors.affiliation: College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju 500-757, South Korea. Electronic address: kwanglee@chonnam.ac.kr.
authors.forename: Kwang Youl
authors.initials: KY
authors.lastname: Lee
mesh_terms: D020816:Amino Acid Motifs; D015536:Down-Regulation; D057809:HEK293 Cells; D006801:Humans; D025821:Polyubiquitin / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011485:Protein Binding; D059748:Proteolysis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D054875:Ubiquitination; D050986:YY1 Transcription Factor / Q000737:chemistry / Q000378:metabolism*
chemical_list: D016159:Tumor Suppressor Protein p53; D050986:YY1 Transcription Factor; C494698:YY1 protein, human; D025821:Polyubiquitin; C471641:SMURF2 protein, human; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex
keywords: Protein stability; Smurf2; Ubiquitination; YY1