Estrogen-dependent transcription of the NEL-like 2 (NELL2) gene and its role in protection from cell death.
NELL2 (neural tissue-specific epidermal growth factor-like repeat domain-containing protein) is a secreted glycoprotein that is predominantly expressed in neural tissues. We reported previously that NELL2 mRNA abundance in brain is increased by estrogen (E2) treatment and that NELL2 is involved in the E2-dependent organization of a sexually dimorphic nucleus in the preoptic area. In this study we cloned the mouse NELL2 promoter and found it to contain two half-E2 response elements. Electrophoretic mobility shift assays and promoter assays showed that E2 and its receptors (ERalpha and ERbeta) stimulated NELL2 transcription by binding to the two half-E2 response elements. Hippocampal neuroprogenitor HiB5 cells expressing recombinant NELL2 showed increased cell survival under cell death-inducing conditions. Blockade of endogenous synthesis of NELL2 in HiB5 cells abolished the cell survival effect of E2 and resulted in a decrease in phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2). These data suggest that the NELL2 gene is trans-activated by E2 and contributes to mediating the survival promoting effects of E2 via intracellular signaling pathway of ERK.
Choi
Eun Jung
EJ
Department of Biological Sciences, University of Ulsan, Ulsan 680-749, South Korea.
Kim
Dong Hee
DH
Kim
Jae Geun
JG
Kim
Dong Yeol
DY
Kim
Jung Dae
JD
Seol
Ok Ju
OJ
Jeong
Choon Soo
CS
Park
Jeong Woo
JW
Choi
Min Young
MY
Kang
Sung Goo
SG
Costa
Maria E
ME
Ojeda
Sergio R
SR
Lee
Byung Ju
BJ
D000818:Animals; D017209:Apoptosis; D016923:Cell Death; D017931:DNA Primers / Q000235:genetics; D004967:Estrogens / Q000378:metabolism*; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000378:metabolism; D051379:Mice; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D020218:Response Elements; D015398:Signal Transduction
D017931:DNA Primers; D004967:Estrogens; C491253:Nell2 protein, mouse; D009419:Nerve Tissue Proteins; D048052:Mitogen-Activated Protein Kinase 3