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J. Biochem, 1994, Vol. 115, No. 2 298-303
© 1994 Japanese Biochemical Society


research-article

Novel Isoforms of Human Cyclic AMP-Responsive Element Modulator (hCREM) mRNA1

Tomoko Fujimoto2, Jun-ichi Fujisawa and Mitsuaki Yoshida

Department of Cellular and Molecular Biology, Institute of Medical Science, The University of Tokyo, 4–6–1 Shirokanedai Minato-ku, Tokyo 108

The cyclic AMP-response element (CRE), a transcriptional enhancer, is regulated by CREB (CRE-binding protein) which is the leucine zipper protein phosphorylated by protein kinase A in response to cAMP signal. The highly homologous protein CREM (CRE-modulator) is thought to modulate CREB-stimulated transcription, and is also involved in transcriptional control during spermatogenesis. In this paper, we report two types of cDNAs of human CREM (hCREM), type 1 and type 2; type 1 is a group of human counterparts of the mouse CREM{alpha} and type 2 is a novel form having a distinct 5' exon which is unrelated to any species of the CREB and CREM isoforms so far described. This unique 5' region of type 2 hCREM may suggest its independent expression from type 1 CREM. The specific 5' region of type 2 hCREM consisted of 88 bp, containing an initiation codon for translation, but no possible phosphorylation site, suggesting different roles from type 1 CREM. Both type 1 and 2 hCREMs are expressed in lymphoid and non-lymphoid cell lines. Their excess expression by transfection induced suppression of cAMP-mediated activation of transcription, suggesting their negative regulation of CRE-mediated transcription.

1This work was supported in part by a grant for Special Project Research, Cancer Bioscience, from the Ministry of Education, Culture and Science of Japan. The sequences described here been submitted to DDBJ under accession numbers D14825 [GenBank] and D14826 [GenBank] .

2Present address: Department of Microbiology, Keio University, School of Medicine, Shinanomachi, Shinjuku-ku, Tokyo 160


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