Isolation, characterization and mapping of the mouse and human RB1CC1 genes
Introduction
We recently identified a novel human gene, RB1CC1 (-inducible oiled-oil : Human Gene Nomenclature Committee-approved gene symbol), during a search for genes implicated in multi-drug resistance (MDR) to anticancer agents (Chano et al., 2002). RB1CC1 expression is associated with the survival of MDR cancer cells treated with anticancer agents. Preliminary experiments also suggest that RB1CC1 may function as a key regulator for RB1 (retinoblastoma 1) expression: RB1CC1 expression correlates closely with that of RB1 in various cancer cell lines and normal human tissues, and introduction of wild-type RB1CC1 induced significant RB1 expression in human leukemic cells (Chano et al., 2002).
Two previous studies have independently identified mouse Rb1cc1 as a cytoplasmic protein with varied functions, however. Maucuer et al. (1995) called Rb1cc1 as Cc1, and reported that it interacts with stathmin, a ubiquitous cytoplasmic protein, and predicted that Cc1 responds to many regulatory signals through its interaction with stathmin. Pfeuffer et al. (2000) called it as LaXp180, and proposed that it binds to the Listeria monocytegenes surface protein ActA, an important virulence factor, in listeriae-infected mammalian cells. These results contradict to our recent study in human. The deduced amino acid sequence of RB1CC1 contains a nuclear localization signal, a leucine zipper motif and a coiled-coil structure, indicating RB1CC1 is a nuclear protein; Immunoblot and immunocytochemical analyses have demonstrated nuclear localization of the human RB1CC1 protein (Chano et al., 2002). It remains to be determined whether the contradiction may result from species difference, or multiple function of RB1CC1; however, clarification of the molecular roles of RB1CC1 is hampered by scarcity of information about the gene. To gain more insight into RB1CC1 function, we have further characterized the human and mouse RB1CC1 genes.
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Rb1cc1 cDNA isolation and sequencing
To clone the complete mouse Rb1cc1 cDNA, we performed a BLAST homology search of public databases using the human RB1CC1 cDNA sequence (GenBank accession no. AB059622) as query sequence. Several mouse clones (accession nos. AW495435, AA497846, AJ242720, AA458361, AW701067) were identified, and primers were designed based on their sequences. cDNAs were synthesized by RT–PCR, using oligo (dT)12–18 primer and C57BL/6 mouse muscle mRNA. The entire Rb1cc1 coding region was amplified using the
Rb1cc1 is the mouse homologue of human RB1CC1
The complete Rb1cc1 cDNA was 6518 bp in length with an open leading frame of 4764 bp, coding 1588 amino acids (accession no. AB070619). The clone was considered to contain a full-length cDNA because: (1) the putative transcription start sites and first methionine were good alignment with its human counterpart RB1CC1; (2) sequence around the putative translation start site (ATC ATC ATG A) was compatible with the Kozak consensus; (3) repeated attempts of 5′-RACE did not yield more 5′ clones; and
Acknowledgements
This study was partially supported by grants-in-aid for JSPS Fellows (No. 4808), Scientific Research (B) (No. 13470520), The Ministry of Education, Science, Sports and Culture of Japan, and a grant from the Japan Orthopaedics and Traumatology Foundation, Inc. (No. 0110).
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