Polo-like kinase 2 gene expression is regulated by the orphan nuclear receptor estrogen receptor-related receptor gamma (ERRgamma).
Estrogen receptor-related receptor gamma (ERRgamma) is a member of the nuclear receptor family of transcriptional activators. To date, the target genes and physiological functions of ERRgamma are not well understood. In the current study, we identify that Plk2 is a novel target of ERRgamma. Northern blot analysis showed that overexpression of ERRgamma induced Plk2 expression in cancer cell lines. ERRgamma activated the Plk2 gene promoter, and deletion and mutational analysis of the Plk2 promoter revealed that the ERRgamma-response region is located between nucleotides (nt) -2327 and -2229 and -441 and -432 (relative to the transcriptional start site at +1). Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) analysis demonstrated that ERRgamma binds directly to the Plk2 promoter. Overexpression of ERRgamma in the presence of the mitotic inhibitor nocodazole significantly decreased apoptosis, and induced S-phase cell cycle progression through the induction of Plk2 expression. Taken together, these results demonstrated that Plk2 is a novel target of ERRgamma, and suggest that this interaction is crucial for cancer cell proliferation.
Park
Yun-Yong
YY
Hormone Research Center, School of Biological Sciences and Technology, Chonnam National University, Gwangju 500-757, Republic of Korea.
Kim
Seok-Ho
SH
Department of Oral Biochemistry, Dental Science Research Institute, School of Dentistry, Chonnam National University, Gwangju 500-757, Republic of Korea.
Kim
Yong Joo
YJ
Department of Chemistry, Seoul National University, Seoul 151-747, Republic of Korea.
Kim
Sun Yee
SY
Section of Endocrinology, Department of Internal Medicine, Kyungpook National University, Taegu 700-721, Republic of Korea.
Lee
Tae-Hoon
TH
Department of Oral Biochemistry, Dental Science Research Institute, School of Dentistry, Chonnam National University, Gwangju 500-757, Republic of Korea.
Lee
In-Kyu
IK
Section of Endocrinology, Department of Internal Medicine, Kyungpook National University, Taegu 700-721, Republic of Korea.
Park
Seung Bum
SB
Department of Chemistry, Seoul National University, Seoul 151-747, Republic of Korea.
Choi
Hueng-Sik
HS
Hormone Research Center, School of Biological Sciences and Technology, Chonnam National University, Gwangju 500-757, Republic of Korea. Electronic address: hsc@chonnam.ac.kr.
D000818:Animals; D019556:COS Cells; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002469:Cell Separation; D002522:Chlorocebus aethiops; D017353:Gene Deletion; D005786:Gene Expression Regulation; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis*; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis* / Q000502:physiology*; D011960:Receptors, Estrogen / Q000096:biosynthesis* / Q000502:physiology*
C490917:ESRRG protein, human; D018160:Receptors, Cytoplasmic and Nuclear; D011960:Receptors, Estrogen; C496126:PLK2 protein, human; D017346:Protein Serine-Threonine Kinases