Disease relevance of RB1CC1

• Truncating mutations of RB1CC1 in human breast cancer [1].
• RB1CC1 is abundantly expressed in human musculoskeletal and cultured osteosarcoma cells [2].
• RB1CC1 expression levels correlated closely with those of RB1 (retinoblastoma 1) in cancer cell lines as well as in various normal human tissues [3].
• All seven G6-positive lymphomas and two G6-negative tumors reacted with Cc1, another MAb specific for a rheumatoid factor heavy-chain-associated CRI [4].

High impact information on RB1CC1

• Wildtype RB1CC1 and RB1 were absent or significantly less abundant than normal in the seven cancers with mutations in RB1CC1, but were abundant in cancers without such mutations [1].
• The gene RB1CC1 is localized to a region of chromosome 8q11 (ref. 2) containing several loci of putative tumor-suppressor genes; however, its role in human cancers remains to be determined [1].
• We found that FIP200 knockout (KO) embryos show reduced S6 kinase activation and cell size as a result of increased tuberous sclerosis complex function [5].
• Together, our results reveal that FIP200 functions as a regulatory node to couple two important signaling pathways to regulate cell growth and survival during mouse embryogenesis [5].
• Furthermore, FIP200 KO embryos exhibited significant apoptosis in heart and liver [5].

Chemical compound and disease context of RB1CC1

• 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 [3].

Biological context of RB1CC1

• Thus, RB1CC1 is frequently mutated in breast cancer and shows characteristics of a classical tumor-suppressor gene [1].
• In addition, the introduction of wild-type RB1CC1 decreased the formation of macroscopic colonies in the cell growth assay [2].
• These data suggest that RB1CC1 may be a key regulator of RB1 gene expression [3].
• The human and mouse RB1CC1 genes, both of which contain 24 exons, span 74 kb on chromosome 8q11.2 and 57 kb on chromosome 1A2-4, respectively [6].
• Conserved sequence motifs and nuclear localization suggest that the RB1CC1 proteins function as transcription factors [6].

Anatomical context of RB1CC1

• The amount of RB1CC1 message was closely related to RB1 expression in various osteosarcoma cell lines [2].
• RB1CC1 expression was difficult to detect in immature proliferating chondroblasts or myogenic cells in human embryos, but became obvious and prominent concomitantly with the maturation of osteocytes, chondrocytes, and skeletal muscle cells [2].
• It is abundant in post-mitotic neuromuscular cells, which are matured and enlarged, but scarce in smaller leukocytes, indicating an association between RB1CC1 status and cell size [7].
• FIP200 is a novel protein inhibitor for focal adhesion kinase (FAK), which binds to FAK directly and inhibits its kinase activity and associated cellular functions, such as cell adhesion, spreading, and motility in fibroblasts [8].
• Regulation of focal adhesion kinase by a novel protein inhibitor FIP200 [9].

Associations of RB1CC1 with chemical compounds

• We also found that the NH2-terminal 154 residues of FIP200 were sufficient to mediate p53 interaction and G1 arrest in cells [8].

Physical interactions of RB1CC1

• Furthermore, we found that FIP200 could interact with exogenous and endogenous p53 protein and significantly increase its half-life compared with the control cells [8].
• FIP200 bound to the kinase domain of Pyk2 and inhibited its kinase activity in in vitro kinase assays [10].

Regulatory relationships of RB1CC1

• Moreover, introduction of wild-type RB1CC1 significantly induced RB1 expression in human leukemic cells [3].

Other interactions of RB1CC1

• Western blotting showed that underphosphorylated forms of RB1 were elicited by RB1CC1, whereas E2F1 was not affected [11].
• 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 [3].
• Together, these results suggest that FIP200 functions as an inhibitor of Pyk2 via binding to its kinase domain [10].

Analytical, diagnostic and therapeutic context of RB1CC1

• Western blot analysis and immunocytochemical staining with anti-RB1CC1 antibody showed that endogenously expressed RB1CC1 protein localized to the nucleus [3].

References