| First Author | Yamamoto M | Year | 2019 |
| Journal | Commun Biol | Volume | 2 |
| Pages | 292 | PubMed ID | 31396572 |
| Mgi Jnum | J:278091 | Mgi Id | MGI:6356165 |
| Doi | 10.1038/s42003-019-0547-7 | Citation | Yamamoto M, et al. (2019) TRAF6 maintains mammary stem cells and promotes pregnancy-induced mammary epithelial cell expansion. Commun Biol 2:292 |
| abstractText | Receptor activator of nuclear factor (NF)-kappaB (RANK) signaling promotes pregnancy-dependent epithelial cell differentiation and expansion for mammary gland development, which requires NF-kappaB pathway-dependent Cyclin D1 induction and inhibitor of DNA binding 2 (Id2) pathway-dependent anti-apoptotic gene induction. However, the roles of tumor necrosis factor receptor-associated factor 6 (TRAF6) remain unclear despite its requirement in RANK signaling. Here we show that TRAF6 is crucial for both mammary stem cell maintenance and pregnancy-induced epithelial cell expansion. TRAF6 deficiency impairs phosphoinositide 3-kinase (PI3K)/AKT and canonical NF-kappaB pathways, whereas noncanonical NF-kappaB signaling remains functional. Therefore, we propose that TRAF6 promotes cell proliferation by activating PI3K/AKT signaling to induce retinoblastoma phosphorylation in concert with noncanonical NF-kappaB pathway-dependent Cyclin D1 induction. Furthermore, TRAF6 inhibits apoptosis by activating canonical NF-kappaB signaling to induce anti-apoptotic genes with the Id2 pathway. Therefore, proper orchestration of TRAF6-dependent and -independent RANK signals likely establishes mammary gland formation. |
