Survival and differentiation of mammary epithelial cells in mammary gland development require nuclear retention of Id2 due to RANK signaling

Nam Shik Kim, Hyoung Tai Kim, Min Chul Kwon, Suk Won Choi, Yoon Young Kim, Ki Jun Yoon, Bon Kyoung Koo, Myung Phil Kong, Juhee Shin, Yunje Cho, Young Yun Kong

Research output: Contribution to journalArticlepeer-review

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 S5ATg 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.

Original languageEnglish (US)
Pages (from-to)4775-4788
Number of pages14
JournalMolecular and cellular biology
Volume31
Issue number23
DOIs
StatePublished - Dec 2011
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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