Disease relevance of Cbx2

• Immunoblots probed with an antibody to M33 protein, a homolog of Drosophila Polycomb, revealed that most M33 in adult mouse liver had a higher electrophoretic mobility than that in F9 embryonal carcinoma cells [1].
• This ability to promote cellular migration suggests a role for viral GPCRs like M33 in viral dissemination in vivo, and accordingly, M33 is required for efficient murine cytomegalovirus replication in the mouse [2].
• In this study, we used recombinant retroviruses to express M33 in wild-type and Galpha(q/11)(-/-) mouse embryonic fibroblasts and show that M33 couples directly to the G(q/11) signaling pathway to induce high levels of total inositol phosphates in an agonist-independent manner [2].
• Sequencing of some immune evasion genes known to be located at the 3' or 5' ends of the MCMV genome showed that no mutations were present in ORFs m04, m06, M33, M37, m38.5, m144, m152, or m157 although mutations were found in M27 (A658S) and M36Ex1 (V54I). tsm5 made few capsids at 40 degrees C and these lacked DNA [3].

High impact information on Cbx2

• Bmi1, M33, and Mph1 show an overlapping speckled distribution in interphase nuclei [4].
• Ring1A represses transcription through sequences not involved in M33 binding [5].
• Furthermore, we have identified two murine proteins, Ring1A and Ring1B, that interact directly with the repressor domain of M33 [5].
• The late replication data are consistent with the measurements of levels of mitochondrial malic enzyme (MOD-2, whose locus is on the autosomal segment) activity in these mice [Eicher E. & Coleman, D. (1977) Genetics 85, 647-658] [6].
• Mouse Polycomb M33 is required for splenic vascular and adrenal gland formation through regulating Ad4BP/SF1 expression [7].

Biological context of Cbx2

• We propose that a function of the M33 protein is to control the accessibility of retinoic acid response elements in the vicinity of Hox genes regulatory regions by direct or indirect mechanisms or both [8].
• Here we report the skeletal phenotypes of compound mutants for two Polycomb group genes bmi1 and M33 [9].
• In addition, M33 null mutant mice show an aggravation of the skeletal malformations when treated to RA at embryonic day 7.5, leading to the hypothesis that, during development, the M33 gene might play a role in defining access to retinoic acid response elements localised in the regulatory regions of several Hox genes [10].
• Here we show that embryonic fibroblasts derived from M33-deficient mice are impaired in the progression into the S phase of the cell cycle, as shown by a reduced rate of incorporation of bromodeoxyuridine [11].
• We show that mouse Polycomb group homologues, RAE28, BMI1 and M33, have overlapping but not identical expression patterns during embryogenesis and in adult tissues [12].

Anatomical context of Cbx2

• Disruption of the murine M33 gene, a PcG member, displayed posterior transformation of the vertebral columns and sternal ribs [7].
• Homozygous M33 (-/-) mice show greatly retarded growth, homeotic transformations of the axial skeleton, sternal and limb malformations and a failure to expand in vitro of several cell types including lymphocytes and fibroblasts [10].
• In addition, we show that the polycomb protein M33 controls critical expansion of B- and T-lymphocyte precursors [11].
• M33 is functionally similar to the human cytomegalovirus-encoded US28 GPCR in its ability to induce inositol phosphate accumulation, activate NF-kappaB, and promote smooth muscle cell migration [2].
• Mouse cytomegalovirus M33 is necessary and sufficient in virus-induced vascular smooth muscle cell migration [13].

Associations of Cbx2 with chemical compounds

• Mouse chimeras were produced from strains which differ in their electrophoretic variants of the nuclear-coded mitochondrial protein, malic enzyme (MOD-2, E.C. 1.1.1.40, L-malate NADP+ oxidoreductase decarboxylating) [14].

Regulatory relationships of Cbx2

• Disruption of E2F signaling suppresses the INK4a-induced proliferative defect in M33-deficient mice [11].

Other interactions of Cbx2

• In agreement with these observations, chromatin immunoprecipitation assays with adrenocortical Y-1 cells revealed direct binding of the M33-containing PcG to the Ad4BP/SF1 gene locus [7].
• The expression of Ring1A at early stages of development is restricted to the neural tube, whereas M33 is expressed ubiquitously [5].
• A further nine recombinants were detected between Ts and the polycomb-like gene M33, suggesting that these loci are separated by 1.8 +/- 0.011 cM [15].
• Sry, Sox9 and M33 are thought to act as architectural transcription factors or as a chromatin regulator in gonadal development [16].
• Here, we report the cloning and characterization of a novel mouse polycomb homolog, MPc2, in addition to the previously described M33 polycomb gene [17].

Analytical, diagnostic and therapeutic context of Cbx2

• By 60 h, most M33 was in the form of these low-mobility species, and the pattern of immunofluorescence suggested the existence of chromatin-bound and free states of the protein in the nucleus [1].
• Gel filtration analysis of embryonic extracts indicates that RAE28, BMI1 and M33 exist in large multimeric complexes [12].

References