Caenorhabditis elegans Elongin BC complex is essential for cell proliferation and chromosome condensation and segregation during mitosis and meiotic division II

Abstract

The ubiquitin-mediated protein degradation system is involved in a wide variety of cellular functions. The RING-H2 finger protein RBX1 is a common subunit of Cullin-based ubiquitin ligases. Caenorhabditis elegans RBX1 and CUL2 are essential for regulating chromosome condensation and segregation during mitosis and meiosis and are also critical for cell proliferation. Here, we demonstrate that Elongin B (ELB1) and C (ELC1) form a stable complex, and that depletion of either gene product by RNA-mediated interference (RNAi) causes pronounced defects in the second meiotic division. Embryos and adults that escape meiotic arrest have several irregular phenotypes. These include defects in mitotic chromosomal condensation and segregation, pronuclear rotation, and germ cell proliferation, abnormal cortical protrusion, and accumulation of the cyclin-dependent kinase inhibitor CKI1. All these defects are consistent with those found after depletion of CUL2. In addition, direct interaction between ELC1 and CUL2 is revealed by bacterial two-hybrid analysis. Thus, the RBX1/CUL2/ELC1/ELB1 complex acts as an E3 ubiquitin ligase in C. elegans and is essential for diverse functions relevant to chromosomal dynamics and cell cycle control.

Degrade to create: developmental requirements for ubiquitin-mediated proteolysis during earlyC. elegansembryogenesis

“…Similar meiosis defects are observed after depletion of RBX-1 or of ELB-1/ELC-1 (Elongin B1/Elongin C1) Sasagawa et al, 2005;Sasagawa et al, 2003). Furthermore, ELB-1 and ELC-1 form a stable complex, and ELC-1 binds CUL-2, indicating that an ECS E3 ligase is required for progression through meiosis II Sasagawa et al, 2005). The meiosis II defects in mutants lacking CUL-2 are not a result of a failure to degrade the meiosis-specific cohesin REC-8 , and thus the targets of CUL-2 during meiosis II remain unknown.…”

“…Loss of CUL-2 function also impairs meiosis in the early embryo, delaying both the onset of meiosis II anaphase and exit from meiosis II Sonneville and Gönczy, 2004). Similar meiosis defects are observed after depletion of RBX-1 or of ELB-1/ELC-1 (Elongin B1/Elongin C1) Sasagawa et al, 2005;Sasagawa et al, 2003). Furthermore, ELB-1 and ELC-1 form a stable complex, and ELC-1 binds CUL-2, indicating that an ECS E3 ligase is required for progression through meiosis II Sasagawa et al, 2005).…”

Caenorhabditis elegans p97 controls germline-specific sex determination by controlling the TRA-1 level in a CUL-2-dependent manner

“…p97 might disassemble the substrate by changing its conformation using ATP-hydrolyzing energy. p97 regulates sperm-oocyte switch cyclin-dependent kinase (CDK) inhibitor CKI-1 degradation, meiotic progression, PAR-6 degradation and the establishment of anteriorposterior polarity, cyclin B1 degradation, chromatin condensation, mitotic progression, proper cytoplasmic organization and the degradation of CCCH-finger polarity proteins such as PIE-1 (Feng et al, 1999;DeRenzo et al, 2003;Liu et al, 2004;Sonneville and Gonczy, 2004;Sasagawa et al, 2005;Sasagawa et al, 2007a;Pacquelet et al, 2008). Importantly, some of the phenotypes observed in the cul-2 mutant, including defects in meiotic progression, chromosome condensation, cyclin B1 degradation, and establishment of anterior-posterior polarity, have also been observed in p97-depleted worms (Sasagawa et al, 2007b) (and our unpublished results).…”

Parathyroid Hormone-Like Hormone (PTHLH) Feedback Mitosis to Downstream DNA Replication Coupling Postreplication Repair-Induced Cell Proliferation Network in No-Tumor Hepatitis/Cirrhotic Tissues (HBV or HCV Infection) by Systems-Theoretical Analysis

“…The relationships of mitosis or double-strand break repair with cell proliferation are presented in some papers. Such as, Daughter cell proliferation despite normal completion of mitosis is blocked by prolonged prometaphase [29]; the timely transit of cells by mitosis and tumor cell proliferation are controlled by phosphorylation of p62 by cdk1 [30]; How mitosis is hijacked to denucleate and modulate cell proliferation and differentiation is revealed by perturbing the ubiquitin pathway in vivo [31]; DNA double-strand break repair genes role in cell proliferation under low dose-rate irradiation conditions [32]; The logic of the Mitosis, Membrane, Magnesium(MMM) model for the regulation of animal cell proliferation [33]; Cell proliferation during mitosis and meiotic division II requires caenorhabditis elegans Elongin BC complex [34]; Cancer cell proliferation at mitosis are inhibited by antimitotic antifungal compound benomyl , by binding to a novel site in tubulin [35]; Blockage of endothelial cell proliferation related to a mitosis arrest inhibits tumor growth in vivo [36]; mitosis counts and immunoreactivity for proliferating cell nuclear antigen (PCNA) determines proliferation in malignant mesothelioma [37]; Failure of tripeptide colon mitosis inhibitor to inhibit the cell proliferation of dimethylhydrazine-induced colonic cancers in rats [38]; An endogenous colon mitosis inhibitor reduces the increased cell proliferation in colonic epithelium induced by dietary cholic acid and treatment with 1,2-dimethylhydrazine [39]; An endogenous colon mitosis inhibitor inhibit the increased colonic cell proliferation induced by cholic acid [40]. Therefore, we proposed PTHLH feedback mitosis to downstream DNA replication coupling postreplication repair-induced cell proliferation in no-tumor hepatitis/cirrhotic tissues.…”