NAPP2, a peroxisomal membrane protein, is also a transcriptional corepressor.
Nuclear factor-erythroid number 2 (NF-E2) is a positive regulatory, DNA binding transcription factor for gene expression in erythroid and megakaryocytic cells. To further understand the mechanisms of NF-E2 function, we used expression cloning to identify coregulators interacting with the erythroid-specific subunit of NF-E2, p45. We have isolated a protein, NAPP2, which contains an aspartic-acid- and glutamic-acid-rich region and a nuclear localization signal. The gene encoding NAPP2, PEX14, is located on chromosome 1p36 and is ubiquitously expressed. The domains of interaction in vitro and in vivo between p45 and NAPP2 were mapped by a yeast two-hybrid system and cotransfection experiments. In mammalian cell culture, ectopically expressed NAPP2 inhibited p45-directed transcriptional activation. Furthermore, NAPP2 functions as a corepressor and interacts specifically with histone deacetylase l (HDAC1), but not HDAC2 or HDAC3. NAPP2 is thus potentially a negative coregulator of NF-E2. NAPP2 is identical to PEX14, an integral membrane protein essential for protein docking onto the peroxisomes. These studies have identified a novel, bifunctional protein capable of acting as a transcriptional corepressor and a polypeptide transport modulator. They also suggest that NF-E2 may function both positively and negatively in the transcription regulation of specific erythroid and megakaryocytic genes.
Gavva
Narender R
NR
Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan, Republic of China.
Wen
Shau-Ching
SC
Daftari
Pratibha
P
Moniwa
Mariko
M
Yang
Wen-Ming
WM
Yang-Feng
Lan-Ping Teresa
LP
Seto
Edward
E
Davie
James R
JR
Shen
Che-Kun James
CK
D000595:Amino Acid Sequence; D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000235:genetics*; D050981:Erythroid-Specific DNA-Binding Factors; D005809:Genes, Regulator; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D008969:Molecular Sequence Data; D050983:NF-E2 Transcription Factor; D050984:NF-E2 Transcription Factor, p45 Subunit; D000074401:Peroxins; D020675:Peroxisomes / Q000737:chemistry / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors / Q000235:genetics*; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D050983:NF-E2 Transcription Factor; D050984:NF-E2 Transcription Factor, p45 Subunit; C494692:NFE2 protein, human; C499195:PEX14 protein, S cerevisiae; C455539:PEX14 protein, human; D000074401:Peroxins; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors