title: Chondrocyte proliferation regulated by secreted luminal domain of ER stress transducer BBF2H7/CREB3L2.
abstract: The endoplasmic reticulum (ER) stress transducer BBF2H7/CREB3L2 is an ER-resident transmembrane transcription factor. In response to physiological ER stress, it is processed at the transmembrane region to generate a cytoplasmic N terminus, which contains a basic leucine zipper (bZIP) domain, and luminal C terminus. The BBF2H7 N terminus functions as a transcription factor to promote the expression of ER-Golgi trafficking-related genes and plays crucial roles in chondrocyte differentiation. Here, we found that the BBF2H7 C terminus is secreted into the extracellular space as a signaling molecule for cell-to-cell communication. The secreted BBF2H7 C terminus directly binds to both Indian hedgehog and its receptor Patched-1, followed by activation of Hedgehog signaling, resulting in promoting the proliferation of neighboring chondrocytes. The dual N- and C-terminal functions of BBF2H7 triggered by physiological ER stress may allow chondrocytes to simultaneously regulate distinct cellular events for differentiation and proliferation in developing cartilage.
authors: Department of Biochemistry, Institute of Biomedical & Health Sciences, University of Hiroshima, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
authors: Atsushi
authors: A
authors: Saito
authors: Department of Biochemistry, Institute of Biomedical & Health Sciences, University of Hiroshima, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
authors: Soshi
authors: S
authors: Kanemoto
authors: Department of Biochemistry, Institute of Biomedical & Health Sciences, University of Hiroshima, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
authors: Yizhou
authors: Y
authors: Zhang
authors: Department of Biochemistry, Institute of Biomedical & Health Sciences, University of Hiroshima, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
authors: Rie
authors: R
authors: Asada
authors: Department of Biochemistry, Institute of Biomedical & Health Sciences, University of Hiroshima, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
authors: Kenta
authors: K
authors: Hino
authors: Department of Biochemistry, Institute of Biomedical & Health Sciences, University of Hiroshima, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan. Electronic address: imaizumi@hiroshima-u.ac.jp.
authors: Kazunori
authors: K
authors: Imaizumi
mesh_terms: D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism*; D002356:Cartilage / Q000166:cytology / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000235:genetics / Q000378:metabolism*; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D017434:Protein Structure, Tertiary
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; C544811:Creb3l2 protein, mouse; D053823:Hedgehog Proteins; C514061:ihh protein, mouse