- 作者: Yuh-Charn Lin, Binay K. Sahoo, Shiang-Shin Gau & Ruey-Bing Yang
- 作者服務機構: 1.Biomedical Translation Research Center, Academia Sinica, Taipei, Taiwan 2.Department of Physiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan 3.Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan 4.Program in Drug Discovery and Development Industry, College of Pharmacy, Taipei Medical University, Taipei, Taiwan
- 中文摘要:
- 英文摘要:
The SCUBE [Signal peptide-Complement C1r/C1s, Uegf, Bmp1 (CUB)-Epithelial growth factor domain-containing
protein] family consists of three proteins in vertebrates, SCUBE1, 2 and 3, which are highly conserved in zebrafsh,
mice and humans. Each SCUBE gene encodes a polypeptide of approximately 1000 amino acids that is organized into
fve modular domains: (1) an N-terminal signal peptide sequence, (2) nine tandem epidermal growth factor (EGF)-like
repeats, (3) a large spacer region, (4) three cysteine-rich (CR) motifs, and (5) a CUB domain at the C-terminus. Murine
Scube genes are expressed individually or in combination during the development of various tissues, including those
in the central nervous system and the axial skeleton. The cDNAs of human SCUBE orthologs were originally cloned
from vascular endothelial cells, but SCUBE expression has also been found in platelets, mammary ductal epithe‑
lium and osteoblasts. Both soluble and membrane-associated SCUBEs have been shown to play important roles in
physiology and pathology. For instance, upregulation of SCUBEs has been reported in acute myeloid leukemia, breast
cancer and lung cancer. In addition, soluble SCUBE1 is released from activated platelets and can be used as a clinical
biomarker for acute coronary syndrome and ischemic stroke. Soluble SCUBE2 enhances distal signaling by facilitating
the secretion of dual-lipidated hedgehog from nearby ligand-producing cells in a paracrine manner. Interestingly, the
spacer regions and CR motifs can increase or enable SCUBE binding to cell surfaces via electrostatic or glycan-lectin
interactions. As such, membrane-associated SCUBEs can function as coreceptors that enhance the signaling activity
of various serine/threonine kinase or tyrosine kinase receptors. For example, membrane-associated SCUBE3 func‑
tions as a coreceptor that promotes signaling in bone morphogenesis. In humans, SCUBE3 mutations are linked to
abnormalities in growth and diferentiation of both bones and teeth. In addition to studies on human SCUBE function,
experimental results from genetically modifed mouse models have yielded important insights in the feld of systems
biology. In this review, we highlight novel molecular discoveries and critical directions for future research on SCUBE
proteins in the context of cancer, skeletal disease and cardiovascular disease - 中文關鍵字:
- 英文關鍵字: Biomarker, Coreceptor, Endothelial cells, Signal transduction, SCUBE