title: Survival and differentiation of mammary epithelial cells in mammary gland development require nuclear retention of Id2 due to RANK signaling.
abstract: RANKL plays an essential role in mammary gland development during pregnancy. However, the molecular mechanism by which RANK signaling leads to mammary gland development is largely unknown. We report here that RANKL stimulation induces phosphorylation of Id2 at serine 5, which leads to nuclear retention of Id2. In lactating Id2Tg; RANKL(-/-) mice, Id2 was not phosphorylated and was localized in the cytoplasm. In addition, in lactating Id2(S5A)Tg mice, Id2(S5A) (with serine 5 mutated to alanine) was exclusively localized in the cytoplasm of mammary epithelial cells (MECs), while endogenous Id2 was localized in the nucleus. Intriguingly, nuclear expression of Id2(S5A) rescued increased apoptosis and defective differentiation of MECs in RANKL(-/-) mice. Our results demonstrate that nuclear retention of Id2 due to RANK signaling plays a decisive role in the survival and differentiation of MECs during mammary gland development.
authors.affiliation: Department of Biological Sciences, Seoul National University, San 56-1, Silim-Dong, Gwanak-Gu, Seoul 151-747, South Korea.
authors.forename: Nam-Shik
authors.initials: NS
authors.lastname: Kim
authors.forename: Hyoung-Tai
authors.initials: HT
authors.lastname: Kim
authors.forename: Min-Chul
authors.initials: MC
authors.lastname: Kwon
authors.forename: Suk-Won
authors.initials: SW
authors.lastname: Choi
authors.forename: Yoon-Young
authors.initials: YY
authors.lastname: Kim
authors.forename: Ki-Jun
authors.initials: KJ
authors.lastname: Yoon
authors.forename: Bon-Kyoung
authors.initials: BK
authors.lastname: Koo
authors.forename: Myung-Phil
authors.initials: MP
authors.lastname: Kong
authors.forename: Juhee
authors.initials: J
authors.lastname: Shin
authors.forename: Yunje
authors.initials: Y
authors.lastname: Cho
authors.forename: Young-Yun
authors.initials: YY
authors.lastname: Kong
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism*; D002470:Cell Survival; D004847:Epithelial Cells / Q000378:metabolism / Q000502:physiology*; D005260:Female; D015870:Gene Expression; D055786:Gene Knockout Techniques; D006801:Humans; D051797:Inhibitor of Differentiation Protein 2 / Q000235:genetics / Q000378:metabolism*; D007774:Lactation; D008297:Male; D008321:Mammary Glands, Animal / Q000166:cytology* / Q000254:growth & development* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D008894:Milk Proteins / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011247:Pregnancy; D021381:Protein Transport; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C497452:Idb2 protein, mouse; D051797:Inhibitor of Differentiation Protein 2; D008894:Milk Proteins; D053246:Receptor Activator of Nuclear Factor-kappa B; D011993:Recombinant Fusion Proteins; C505687:Tnfrsf11a protein, mouse