JEM-1, A NOVEL GENE ENCODING A LEUCINE-ZIPPER NUCLEAR FACTOR UP-REGULATED DURING RETINOID-INDUCED MATURATION OF NB4 PROMYELOCYTIC LEUKEMIA

Retinoid-induced proliferation causing hyperleukocytosis is a severe c omplication of retinoid therapy in t(15;17) acute promyelocytic leukae mia. The molecular basis of this phenomenon is unknown. It is possible that the transiently enhanced cell proliferation results from RA-indu ction of growth regulatory genes. Using Differential Display of cDNAs from NB4 cells we have identified Jem, a novel gene transcript which i s 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 sequen ce 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 pe ptide sequence shows a 'leucine-zipper' dimerisation motif with limite d homology to Fos/Jun and ATF/CREB proteins and several putative phosp horylation sites. An atypical basic region may correspond to an unknow n DNA-binding domain. The C-terminal end of Jem spans a long stretch f eaturing a PEST motif. After transfection into COS cells, the Jem prot ein shows a ponctuated nuclear localisation. We hypothesise that this novel nuclear factor may act as a transcription factor, or coregulator , involved in either cell growth control and/or maturation.