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Nucleic Acids Research, 2001, Vol. 29, No. 6 1308-1316
© 2001 Oxford University Press

Molecular cloning of Ian4: a BCR/ABL-induced gene that encodes an outer membrane mitochondrial protein with GTP-binding activity

Laurence Dahéron, Thorsten Zenz, Linda D. Siracusa, Charles Brenner and Bruno Calabretta*

Thomas Jefferson University, Department of Microbiology and Immunology, Kimmel Cancer Institute, Philadelphia, PA 19107, USA

Using the representation difference analysis technique, we have identified a novel gene, Ian4, which is preferentially expressed in hematopoietic precursor 32D cells transfected with wild-type versus mutant forms of the Bcr/Abl oncogene. Ian4 expression was undetectable in 32D cells transfected with v-src, oncogenic Ha-ras or v-Abl. Murine Ian4 maps to chromosome 6, 25 cM from the centromere. The Ian4 mRNA contains two open reading frames (ORFs) separated by 5 nt. The first ORF has the potential to encode for a polypeptide of 67 amino acids without apparent homology to known proteins. The second ORF encodes a protein of 301 amino acids with a GTP/ATP-binding site in the N-terminus and a hydrophobic domain in the extreme C-terminus. The IAN-4 protein resides in the mitochondrial outer membrane and the last 20 amino acids are necessary for this localization. The IAN-4 protein has GTP-binding activity and shares sequence homology with a novel family of putative GTP-binding proteins: the immuno-associated nucleotide (IAN) family.

* To whom correspondence should be addressed at: Kimmel Cancer Institute, Bluemle Life Sciences Building, 233 South 10th Street, Room 630, Philadelphia, PA 19107, USA. Tel: +1 215 503 4522; Fax: +1 215 923 0249; Email: b_calabretta{at}lac.jci.tju.edu


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