Identification of RB1CC1, a novel human gene that can induce RB1 in various human cells

Abstract

Multidrug resistance to anti-cancer agents (MDR) is a major barrier to successful cancer treatment. Current knowledge about genes that contribute to MDR is limited, however, and its mechanisms remain unclear. To identify genes involved in MDR, we performed differential display analysis and isolated a novel human gene, RB1CC1 (RBI-inducible Coiled-Coil 1). The 6.6-kb RB1CC1 cDNA encodes a putative 1594-amino-acid protein that contains a nuclear localization signal, a leucine zipper motif and a coiled-coil structure. Western blot analysis and immunocytochemical staining with anti-RB1CC1 antibody showed that endogenously expressed RB1CC1 protein localized to the nucleus. In MDR variants of human osteosarcoma cells, RB1CC1 expression increased in response to doxorubicin-induced cytotoxic stress and remained elevated for the duration of drug treatment. RB1CC1 expression levels correlated closely with those of RB1 (retinoblastoma 1) in cancer cell lines as well as in various normal human tissues. Moreover, introduction of wild-type RB1CC1 significantly induced RB1 expression in human leukemic cells. These data suggest that RB1CC1 may be a key regulator of RB1 gene expression.

Genetic networks responsive to sodium butyrate in colonic epithelial cells

“…3), suggesting that this network may be correlated with the colonic cell differentiation induced by SB. Indeed, PMP22 [29], RB1 [30], NDRG1 [31], IGF2R [32], IGF2 [33], JUNB [34], TIMP1 [35] and THRA [36] have been reported to be expressed in the small intestine or colon. This network includes IGF2 at its center.…”

Drosophila Fip200 is an essential regulator of autophagy that attenuates both growth and aging

“…For instance, Fip200 may interact with many important signaling molecules other than Atg1 and Atg13, such as Fak, Rbf and p53, like its mammalian homolog. [32][33][34] On the other hand, Atg1 also has autophagy-independent functions, especially in neurons, where it controls axonal transport, growth and projection. 12 Correspondingly, Atg1 mutation in Drosophila produces strong pleiotropic phenotypes including diminished autophagic activities, cell growth enhancement and defects in axonal transport and projection.…”

FIP200, a key signaling node to coordinately regulate various cellular processes

“…FIP200 was shown to inhibit Pyk2 kinase activity and negatively regulate Pyk2 functions [3]. In 2002, FIP200 has also been independently identified as a potential regulator of the RB1 gene (designated by this group as RB1CC1 for RB1-inducible coiled-coil 1) by Dr. Chano and his colleagues [4]. Prior to these studies, the full length cDNA for FIP200 was already isolated (named as KIAA0203), but without any further characterization or any functions ascribed to it, in projects of sequencing human cDNA clones which correspond to long transcripts in the mid-90's [5].…”

“…Finally, it seems that FIP200 plays very diverse biochemical functions with different binding partners (Table 1). FIP200 functions to directly inhibit FAK and Pyk2 kinase activities [3,13], disrupt TSC1-TSC2 complex formation [11], regulate p53 and TSC1 protein stability [14,15], serve as a scaffolding to facilitate TRAF2-ASK1 signaling to JNK activation [12], and regulate the transcription of Rb1 when localizing in nucleus [4]. Since most of these binding partners associate with different regions of FIP200 (Figure 1), it is possible that FIP200 can exert multiple biochemical functions through different domains.…”