Involvement of RNA binding proteins AUF1 in mammary gland differentiation.
The expression of many genes, such as beta-casein, c-myc, and cyclin D1, is altered by lactogenic hormone stimulation during mammary epithelial cell differentiation. Here, we demonstrate that post-transcriptional regulation plays an important role to establish gene expression required to initiate milk production as well as transcriptional control. AUF1 protein, a member of the AU-rich element (ARE)-binding protein family, plays a role in ARE-mRNA turnover by regulating mRNA stability and/or translational control. Cytoplasmic localization of AUF1 protein is critically linked to function. We show that as the mammary gland differentiates, AUF1 protein moves from the cytoplasm to the nucleus. Moreover, in mammary gland epithelial cells (HC11), stimulation by lactogenic hormone decreased cytoplasmic and increased nuclear AUF1 levels. Direct binding of AUF1 protein was observed on c-myc mRNA, but not beta-casein or cyclin D1 mRNA. AUF1 downregulation in HC11 cells increased the expression of beta-casein mRNA and decreased the expression of c-myc mRNA by lactogenic hormone. Conversely, overexpression of AUF1 inhibited these effects of lactogenic hormone stimulation in HC11 cells. These results suggest that AUF1 participates in mammary gland differentiation processes under the control of lactogenic hormone signals.
Nagaoka
Kentaro
K
Laboratory of Animal Breeding, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Tokyo, Japan. akenaga@mail.ecc.u-tokyo.ac.jp
Tanaka
Tetsuya
T
Imakawa
Kazuhiko
K
Sakai
Senkiti
S
D000818:Animals; D000954:Antigens, Surface / Q000032:analysis / Q000378:metabolism; D002364:Caseins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D005260:Female; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D / Q000032:analysis / Q000378:metabolism*; D008321:Mammary Glands, Animal / Q000737:chemistry / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D011388:Prolactin / Q000378:metabolism / Q000494:pharmacology; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000032:analysis / Q000378:metabolism
D000954:Antigens, Surface; D002364:Caseins; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; C000630986:HNRNPD protein, human; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D; C000630987:Hnrpd protein, mouse; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D019938:Cyclin D1; D011388:Prolactin