Disease relevance of Ring1

• An oncogenic form of Cbl was recently identified in the 70Z/3 pre-B cell lymphoma which has a small deletion at the N-terminus of the Ring finger domain [1].

High impact information on Ring1

• Ring1A and Ring1B display blocks of similarity throughout their sequences, including an N-terminal RING finger domain [2].
• Ring1A represses transcription through sequences not involved in M33 binding [2].
• Within the neural tube, Ring1A RNA is located at the rhombomere boundaries of the hindbrain [2].
• Both Ring1A(-/-)and Ring1A(+/-) mice show anterior transformations and other abnormalities of the axial skeleton, which indicates an unusual sensitivity of axial skeleton patterning to Ring1A gene dosage [3].
• These are either dependent on the phosphotyrosine binding domain of c-Cbl that directly binds to the EGFR or on the region C-terminal of the Ring finger, which allows for indirect binding to an alternative site on the receptor [4].

Biological context of Ring1

• We find that the penetrance of some of these alterations was reduced in mice that are deficient in the class II PcG gene Ring1/Ring1A, indicating a genetic interaction between those two genes [5].
• On the inactive X chromosome, uH2A was maintained in Ring1A or Ring1B null cells, but not in double knockout cells, demonstrating an overlapping function for these proteins in development [6].
• Polycomb group proteins Ring1A/B link ubiquitylation of histone H2A to heritable gene silencing and X inactivation [6].
• RING finger (C3HC4-type zinc finger) is a variant zinc finger motif present in a large family of functionally distinct proteins [7].
• It comprises 12 exons and encodes a putative protein of 496 amino acid residues which shares an overall 67% identity with its human ortholog; it also shares 70% of amino acid identity with mouse CBL over their conserved SH2 and Ring finger domains [8].

Co-localisations of Ring1

• Immunofluorescent staining by the antibodies has shown that endogenous Ring1B proteins clearly co-localize with Ring1A at the pattern of diffuse nuclear speckles [9].

Other interactions of Ring1

• Homeotic transformations of the axial skeleton of YY1 mutant mice and genetic interaction with the Polycomb group gene Ring1/Ring1A [5].
• The expression of Ring1A at early stages of development is restricted to the neural tube, whereas M33 is expressed ubiquitously [2].

References