Colostrinin-driven neurite outgrowth requires p53 activation in PC12 cells.
1. Colostrinin (CLN) induces maturation and differentiation of murine thymocytes, promotes proliferation of peripheral blood leukocytes, induces immunomodulator cytokines, and ameliorates oxidative stress-mediated activation of c-Jun NH2-terminal kinases. 2. Here we report that upon treatment with CLN, medullary pheochromocytoma (PC12) cells ceased to proliferate and extend neurites. 3. The arrest of CLN-treated PC12 cells in the G1 phase of the cell cycle was due to an increase in the phosphorylation of p53 at serine(15) (p53ser15) and expression of p21WAF1. PC12 cells treated with inhibitory oligonucleotides to p53 lacked p53ser15 and p21WAF1 expression, and did not show morphological changes after CLN exposure. Transfection with inhibitory oligonucleotides to p21WAF1 had no effect on p53 activation; however, cells failed to arrest or extend neurites. An oligonucleotide inhibiting luciferase expression had no effect on CLN-mediated p53 activation, p21WAF1 expression, growth arrest, or neurite outgrowth. 4. We conclude that CLN induces delicate cassettes of signaling pathways common to cell proliferation and differentiation, and mediates activities that are similar to those of hormones and neurotrophins, leading to neurite outgrowth.
Bacsi
Attila
A
Department of Microbiology and Immunology, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA.
Stanton
G John
GJ
Hughes
Thomas K
TK
Kruze
Marian
M
Boldogh
Istvan
I
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D019922:GAP-43 Protein / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D016501:Neurites / Q000187:drug effects* / Q000502:physiology*; D016716:PC12 Cells; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D050759:Cyclin-Dependent Kinase Inhibitor p21; D019922:GAP-43 Protein; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D016159:Tumor Suppressor Protein p53; C105874:colostrinine