A potential role for PTTG/securin in the developing human fetal brain.
Human securin, known also as PTTG, has established oncogenic and cell cycle regulatory functions. PTTG/securin transforms cells in vitro, inhibits sister chromatid separation, and regulates secretion of fibroblast growth factor-2. FGF-2 is a key regulator of CNS development and PTTG/securin expression has been reported in murine fetal brain. We examined the expression and function of securin and FGF-2 in the developing human fetal brain and in a fetal neuronal cell line (NT 2). Securin expression was significantly reduced in first and second trimester fetal cerebral cortex compared with adult cerebral cortex, where immunocytochemistry revealed intense securin staining in neuronal cell bodies. FGF-2 protein was concordantly lower in fetal cortex, whereas pretranslational expression of PTTG binding factor (PBF) was not significantly altered in fetal brain compared with adult. PCNA expression demonstrated that high securin levels in adult cortex were associated with absent cell proliferation. In NT-2 cells, securin stimulated FGF-2 expression, which could be abrogated by a carboxyl-terminal mutation. Low transient expression of securin resulted in a significant proliferative effect, whereas high levels of securin expression inhibited cell turnover. We propose a potential role for human PTTG/securin in modulating cell proliferation and FGF-2 expression during human neurogenesis.
Boelaert
K
K
Division of Medical Sciences, University of Birmingham, Queen Elizabeth Hospital, Birmingham, B15 2TH, UK.
Tannahill
L A
LA
Bulmer
J N
JN
Kachilele
S
S
Chan
S Y
SY
Kim
D
D
Gittoes
N J L
NJ
Franklyn
J A
JA
Kilby
M D
MD
McCabe
C J
CJ
D001921:Brain / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D001923:Brain Chemistry; D002455:Cell Division; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005314:Embryonic and Fetal Development; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics / Q000378:metabolism; D064249:Securin; D015854:Up-Regulation
D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; C112633:PTTG1IP protein, human; D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor; D064249:Securin; C578002:pituitary tumor-transforming protein 1, human; D016222:Fibroblast Growth Factor 2; C496348:FGFR1 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1