Modulation of p36 gene expression in human neuronal cells.
p36 is a calcium/lipid-binding phosphoprotein that is expressed at high levels in proliferating and transformed cells, and at low levels in terminally differentiated cells, such as CNS neurons. The calcium-dependent binding to membrane phospholipids, and its capacity to interact with intermediate filament proteins suggest that p36 may be involved in the transduction of extracellular signals. The present work examines p36 gene expression in the mature CNS, primary primitive neuroectodermal tumors (PNETs), and transformed PNET cell lines. p36 immunoreactivity was not observed in normal adult human brain, but low levels of the protein were detected by Western blot analysis. Following acute anoxic cerebral injury, the mean levels of p36 protein were elevated two-fold, and injured neurons exhibited increased p36 immunoreactivity. This phenomenon was likely to have been mediated by post-transcriptional mechanisms since there was no corresponding change in the level p36 mRNA. p36 immunoreactivity was detected in 8 of 9 primary PNETs, and in 3 of 3 neurofilament-expressing PNET cell lines. The levels of p36 protein in PNET cell lines were 5-fold higher than in adult human brain tissue. Although p36 gene expression was generally high in proliferating PNET cells, the levels of p36 mRNA and protein were not strictly correlated with DNA synthesis. Instead, p36 gene expression was modulated in both proliferating and non-proliferating PNET cell cultures by treatment with 50 mIU/ml of insulin, 100 mM ethanol, or 5 microM retinoic acid. The frequent discordances observed experimentally and in vivo between p36 mRNA and p36 protein expression suggest that the steady-state levels of p36 protein in neuronal cells may be regulated primarily by post-transcriptional mechanisms.
de la Monte
S M
SM
Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Charlestown 02129, USA.
Bhavani
K
K
Xu
Y Y
YY
Puisieux
A
A
Wands
J R
JR
D000328:Adult; D000818:Animals; D017306:Annexin A2 / Q000096:biosynthesis* / Q000235:genetics; D001254:Astrocytoma / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D002545:Brain Ischemia / Q000378:metabolism*; D001932:Brain Neoplasms / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005909:Glioblastoma / Q000473:pathology; D005910:Glioma / Q000473:pathology; D006801:Humans; D002534:Hypoxia, Brain / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology; D008563:Membrane Lipids / Q000378:metabolism; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D016501:Neurites / Q000187:drug effects / Q000648:ultrastructure; D009447:Neuroblastoma / Q000473:pathology; D018242:Neuroectodermal Tumors, Primitive / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D014158:Transcription, Genetic; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D017306:Annexin A2; D007328:Insulin; D008563:Membrane Lipids; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D000431:Ethanol; D014212:Tretinoin