Disease relevance of RAD21

• RAD21 and KIAA0196 at 8q24 are amplified and overexpressed in prostate cancer [1].
• Two genes from chromosomal region 8q24-RAD21 and KIAA0196-showed increased expression in clinical prostate carcinomas and were also amplified in 30-40% of xenografts and hormone-refractory tumors [1].
• A genome-wide case-control association study done in our laboratory has identified a single nucleotide polymorphism located in RAD21 as being significantly associated with breast cancer susceptibility [2].
• Correlation of invasion and metastasis of cancer cells, and expression of the RAD21 gene in oral squamous cell carcinoma [3].
• Our findings indicate that the RAD21 gene was closely related to the invasion and metastasis of cancer cells [3].

High impact information on RAD21

• Separation of sister chromatids in anaphase is mediated by separase, an endopeptidase that cleaves the chromosomal cohesin SCC1 [4].
• Mapping of hRAD21, SNF2h and Mi2 binding sites by chromatin immunoprecipitation experiments reveals the specific association of these three proteins with human DNA elements containing Alu sequences [5].
• Nuclear matrix attachment regions (MARs) are regulatory DNA sequences that are important for higher-order chromatin organization, long-range enhancer function, and extension of chromatin modifications [6].
• Immunocytochemical analysis revealed abnormalities in the localization of two heterochromatin proteins, Rad21 cohesin protein and BubR1 checkpoint protein, but the localization of core kinetochore proteins such as centromere protein (CENP)-A and -C was normal [7].
• Azotobacter chroococcum MCD1 contains a cluster of nitrogen fixation (nif) genes coding for the structural polypeptides for nitrogenase (nifH for the Fe-protein and nifD and nifK for the MoFe protein) and a second sequence in the genome homologous to nifH [8].

Chemical compound and disease context of RAD21

• Suppression of RAD21 gene expression decreases cell growth and enhances cytotoxicity of etoposide and bleomycin in human breast cancer cells [2].
• Nuclear matrix targeting of the protein kinase CK2 signal as a common downstream response to androgen or growth factor stimulation of prostate cancer cells [9].
• Nuclear matrix isolated from adenovirus-infected HeLa cells retained bound adenovirus DNA even when washed with 1 M guanidine hydrochloride; this interaction could be inhibited by added purified pTP protein [10].
• PURPOSE: The purpose of this study was to determine whether curcumin would trigger cell death in the head and neck squamous cell carcinoma (HNSCC) cell lines CCL 23, CAL 27, and UM-SCC1 in a dose-dependent fashion [11].
• Three human cancer cell lines (SK-N-SH neuroblastoma and SCC-1 and CAL-27 squamous cell carcinoma of the head and neck), along with OGF and the opioid antagonist naltrexone (NTX) at a dosage (10(-6) M) known to repress or increase, respectively, cell replication, were utilized [12].

Biological context of RAD21

• RAD21 is a component of the cohesin complex that holds sister chromatids together during mitosis and repairs double-strand DNA breaks [13].
• Caspase proteolysis of the cohesin component RAD21 promotes apoptosis [13].
• Interestingly, RAD21 is cleaved by a caspase-like Esp1/separase at the onset of anaphase to trigger sister chromatid separation [13].
• We also demonstrate that caspase proteolysis of RAD21 precedes apoptotic chromatin condensation and has important functional consequences, viz. the partial removal of RAD21 from chromatin and the production of a proapoptotic carboxyl-terminal cleavage product that amplifies the cell death signal [13].
• We studied replacement of the mitotic by the meiotic cohesin complex during mouse germinal cell maturation, and we show that mammalian STAG2 and Rad21 are also involved in several meiosis stages [14].

Anatomical context of RAD21

• Mitotic cohesin subunit RAD21 is also found in fibers that decorate the SC during prophase I in mouse oocytes, suggesting a role for this cohesin in mammalian sister chromatid cohesion in female meiosis [15].
• To determine whether suppression of RAD21 expression influences cellular proliferation, RNA interference technology was used in breast cancer cell lines MCF-7 and T-47D [2].
• Nuclear matrix proteins as structural and functional components of the mitotic apparatus [16].
• Elevated expression of mHR21sp in testis and thymus supports a possible role for the rad21 mammalian homologs in V(D)J and meiotic recombination, respectively [17].
• Indirect immunofluorescence staining also showed nuclear and nuclear matrix localization of the NXP-1 [18].

Associations of RAD21 with chemical compounds

• Moreover, MCF-7 cell sensitivity to two DNA-damaging chemotherapeutic agents, etoposide and bleomycin, was increased after inhibition of RAD21 expression with a dose reduction factor 50 (DRF50) of 1.42 and 3.71, respectively [2].
• In 6 of the 19 patients, a thymidine (T) to cytosine (C) transition was detected at position 1440 of the hHR21 open reading frame (T1440C) [19].
• Nuclear matrix acceptor binding sites for steroid hormone receptors: a candidate nuclear matrix acceptor protein [20].
• Inhibition of nitrogenase by nitrate (nitrite) did not take place in A. chroococcum MCD1, which is unable to assimilate either [21].
• CONCLUSIONS: Single agent oral fusaric acid (1 mg/mL) is an inhibitor of UM-SCC-1 in a murine model [22].

Physical interactions of RAD21

• Nuclear matrix binding regulates SATB1-mediated transcriptional repression [23].
• Nuclear matrix-bound RB was detectable in all cases, indicating that loss of RB is not responsible for decreased class II expression in these lines [24].

Enzymatic interactions of RAD21

• Here, we demonstrate that human RAD21 is preferentially cleaved at Asp(279) by caspases-3 and -7 in vitro to generate two major proteolytic products of approximately 65 and 48 kDa [13].

Other interactions of RAD21

• The data suggest that KIAA0196 and possibly RAD21 are putative target genes for the common amplification of 8q23-24 in prostate cancer [1].
• The cohesin multiprotein complex containing SMC1, SMC3, Scc3 (SA), and Scc1 (Rad21) is required for sister chromatid cohesion in eukaryotes [25].
• The DIF1 gene of Arabidopsis is required for meiotic chromosome segregation and belongs to the REC8/RAD21 cohesin gene family [26].
• In contrast, the levels of securin and Rad21 proteins were not increased in hormone-stimulated p53-null compared with WT cells [27].
• Nuclear matrix association of the human beta-globin locus utilizing a novel approach to quantitative real-time PCR [28].

Analytical, diagnostic and therapeutic context of RAD21

• In this study, the relevance of RAD21 gene expression to the invasion and metastasis of oral squamous cell carcinoma was clarified using laser microdissection and real-time polymerase chain reaction (PCR) [3].
• Reverse transcriptase-polymerase chain reaction (RT-PCR) was performed to amplify the hHR21 gene, and the DNA product was sequenced to identify any genetic abnormalities [19].
• Northern blot analysis, cell survival, and growth assays were performed on control cells and cells with hHR21 variants, and a restriction digest assay was developed to screen for carriers of a detected gene variant [19].
• Western blot analysis with anti-NXP-1 polyclonal antibody showed nuclear matrix localization of NXP-1 in HeLa cells [18].
• However, centromere cohesion was maintained before anaphase in Rad21-depleted cells, and the primary constrictions at centromeres were indistinguishable from those in control cells [29].

References