Identification of NEEP21, encoding neuron-enriched endosomal protein of 21 kDa, as a transcriptional target of tumor suppressor p53.
NEEP21, also designated D4S234E or NSG1, is an endosomal protein expressed in neuronal cells under normal conditions. Here, we report that NEEP21 is a direct transcriptional target gene of the tumor suppressor p53. NEEP21 expression is inducible in non-neuronal human cancer cell lines by exposure to adriamycin, hydrogen peroxide, UV and γ-ray in a p53-dependent manner. Chromatin immunoprecipitation assay indicated that a potential p53-binding site (p53BS) is located in intron 1 of the NEEP21 gene. A reporter assay confirmed that p53BS has p53-responsive activity. The heterologous luciferase gene containing p53BS is also transactivated by p73-β and p63-γ. The introduction of the NEEP21 gene into various cancer cell lines suppressed cell growth. Infection with an adenovirus vector containing NEEP21 induced apoptotic cell death via caspase-3 activation in many cancer cell lines. The expression of NEEP21 mRNA was remarkably induced by γ-ray irradiation in the spleen of p53+/+ mice but not in that of p53-/- mice. These results suggest that NEEP21 may play a critical role in apoptosis as a mediator of p53.
Ohnishi
Shiho
S
Cancer Medicine and Biophysics Division, National Cancer Center Research Institute, Chuo-ku, Tokyo 104-0045, Japan.
Futamura
Manabu
M
Kamino
Hiroki
H
Nakamura
Yasuyuki
Y
Kitamura
Noriaki
N
Miyamoto
Yuji
Y
Miyamoto
Takafumi
T
Shinogi
Daisuke
D
Goda
Olga
O
Arakawa
Hirofumi
H
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D002469:Cell Separation; D047369:Chromatin Immunoprecipitation; D005434:Flow Cytometry; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015533:Transcriptional Activation / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D002352:Carrier Proteins; C553327:NSG1 protein, human; D009419:Nerve Tissue Proteins; D016159:Tumor Suppressor Protein p53