13q deletion in chronic lymphocytic leukemia: characterization of E4.5, a novel chromosome condensation regulator-like guanine nucleotide exchange factor.
We report the characterization of a new gene (E4.5) that maps at chromosome band 13q14.3, a chromosomal area frequently deleted in chronic lymphocytic leukemia (CLL) and in other lymphoid malignancies. E4.5 gene encodes for a 4 kb mRNA expressed in various tissues and has an open reading frame of 531 amino acids. The predicted E4.5 protein shows strong homology with the human regulator of chromosome condensation (RCC1) protein, the principal GTP exchange factor for Ran protein. The E4.5 protein contains a BTB domain in its N-terminus, a protein-protein interaction motif. Therefore, we propose that E4.5 is a new member of the RCC1-related guanine nucleotide exchange factor (GEF) family with potent interaction with other proteins and unknown function. Until now, no tumor suppressor genes have been mapped in the 13q14.3 minimal deleted region (MDR) in patients with CLL. It has been proposed that loss of the 13q14.3 MDR may contribute to lymphoid neoplasia by altering the expression/function of genes located on 13q14.3 outside the MDR. The E4.5 is one of these genes with a potential role in the pathogenesis of CLL.
Solomou
E E
EE
First Department of Propedeutic Medicine, University of Athens Medical School, Laikon General Hospital, 17, Agiou Thoma St., Goudi, Athens, Greece.
Sfikakis
P P
PP
Kotsi
P
P
Papaioannou
M
M
Karali
V
V
Vervessou
E
E
Hoffbrand
A V
AV
Panayiotidis
P
P
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001483:Base Sequence; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002872:Chromosome Deletion; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics*; D018076:DNA, Complementary / Q000235:genetics; D016147:Genes, Tumor Suppressor; D020662:Guanine Nucleotide Exchange Factors / Q000737:chemistry / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics*; D008969:Molecular Sequence Data; D005810:Multigene Family; D016366:Open Reading Frames / Q000235:genetics; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000235:genetics; D017386:Sequence Homology, Amino Acid
D018076:DNA, Complementary; D020662:Guanine Nucleotide Exchange Factors; C482643:RCBTB1 protein, human; D012333:RNA, Messenger