JEM-1, a novel gene encoding a leucine-zipper nuclear factor upregulated during retinoid-induced maturation of NB4 promyelocytic leukaemia.
Retinoid-induced proliferation causing hyperleukocytosis is a severe complication of retinoid therapy in t(15;17) acute promyelocytic leukaemia. The molecular basis of this phenomenon is unknown. It is possible that the transiently enhanced cell proliferation results from RA-induction of growth regulatory genes. Using Differential Display of cDNAs from NB4 cells we have identified Jem, a novel gene transcript which is upregulated by retinoids during the early proliferative response in maturating cells but not in resistant cells. A 2.7 kb cDNA was cloned and sequenced. The open reading frame contains a 400 amino acid sequence corresponding to a novel 45 kDa basic protein (pI 8.9). The JEM DNA sequence is detected by FISH on human chromosome 1 at q24. The Jem peptide sequence shows a 'leucine-zipper' dimerisation motif with limited homology to Fos/Jun and ATF/CREB proteins and several putative phosphorylation sites. An atypical basic region may correspond to an unknown DNA-binding domain. The C-terminal end of Jem spans a long stretch featuring a PEST motif. After transfection into COS cells, the Jem protein shows a ponctuated nuclear localisation. We hypothesise that this novel nuclear factor may act as a transcription factor, or a coregulator, involved in either cell growth control and/or maturation.
Duprez
E
E
Institut National de la Santé et de la Recherche Médical, INSERM-U301, Centre G, Hayem, Hôpital Saint-Louis, Paris, France.
Tong
J H
JH
Dérré
J
J
Chen
S J
SJ
Berger
R
R
Chen
Z
Z
Lanotte
M
M
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D019556:COS Cells; D002467:Cell Nucleus / Q000737:chemistry; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D003001:Cloning, Molecular; D018076:DNA, Complementary; D019281:Dimerization; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D016350:Leucine Zippers; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000032:analysis / Q000737:chemistry / Q000235:genetics*; D010766:Phosphorylation; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000032:analysis / Q000737:chemistry / Q000235:genetics*; D014158:Transcription, Genetic; D014162:Transfection; D014212:Tretinoin / Q000494:pharmacology*
C105528:BLZF1 protein, human; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D018076:DNA, Complementary; D009687:Nuclear Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D014157:Transcription Factors; D014212:Tretinoin