CREBZF, a novel Smad8-binding protein.
Smads are the secondary messengers of the transforming growth factor-β (TGF-β) signaling pathway. TGF-β receptors phosphorylate the Receptor Smads (R-Smads) upon ligand binding; activated R-Smads translocate to the nucleus and function as transcription factors. Among the R-Smads, Smads 1, 5, and 8 mainly mediate signals in the bone morphogenetic proteins (BMPs) pathways, while Smads 2/3 mediate TGF-β signaling. The regulation of Smads in the TGF-β signal pathway has been well defined, but the relationship of Smads 1, 5, and 8 to the BMP pathways has been relatively understudied. To understand the specific regulation of BMP mediating Smads, we performed yeast two-hybrid screening using the Mad homology 2(MH2) domain of Smad8 as bait. In this screening, novel Smad-binding protein, CREBZF-a basic region-leucine zipper (bZIP) transcription factor-was identified. The interaction of CREBZF and Smads 1, 5, and 8 was confirmed by immunoprecipitation in a  human prostate cancer cell line. Overexpression of CREBZF inhibited the promoter activity of BMP response element and abolished the cell growth inhibition induced by BMP-6. Thus, CREBZF inhibits the function of BMP-6 by interacting with Smads. The identification of this novel Smads-binding protein, among others will help us understand the modulation of BMP-signaling pathways.
Section of Urologic Oncology and the Dean and Betty Gallo Prostate Cancer Center, The Cancer Institute of New Jersey and Robert Wood Johnson Medical School, New Brunswick, NJ 08903, USA.
Jae-Ho
JH
Lee
Geun Taek
GT
Lee
Seok Joo
SJ
Kwon
Jeongyun
J
Jeong
Yun-Sok
YS
Ha
Wun-Jae
WJ
Kim
Isaac Yi
IY
Kim
D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism*; D055418:Bone Morphogenetic Protein 6 / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D011401:Promoter Regions, Genetic / Q000502:physiology*; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology*; D051898:Smad1 Protein / Q000235:genetics / Q000378:metabolism; D051899:Smad2 Protein / Q000235:genetics / Q000378:metabolism; D051904:Smad8 Protein / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
C525816:BMP6 protein, human; D050976:Basic-Leucine Zipper Transcription Factors; D055418:Bone Morphogenetic Protein 6; C411104:CREBZF protein, human; C497399:SMAD1 protein, human; C497782:SMAD2 protein, human; C107514:SMAD9 protein, human; D051898:Smad1 Protein; D051899:Smad2 Protein; D051904:Smad8 Protein; D016212:Transforming Growth Factor beta