Splice variants of the nuclear dot-associated Sp100 protein contain homologies to HMG-1 and a human nuclear phosphoprotein-box motif

Sp100 and PML are interferon-inducible proteins associated with a new class of nuclear domains (known as nuclear dots or PML bodies) which play a role in tumorigenesis, virus infections, and autoimmunity. While PML is extensi vely alternatively spliced, only two splice variants are known for Sp100, H ere we describe the identification and characterization of several Sp100 sp lice variant proteins and support their existence by elucidation of the 3'- end of the Sp100 gene. Some of the splice variants contain a domain of sign ificant sequence similarity with two previously described highly related in terferon-inducible nuclear phosphoproteins as well as to suppressin and DEA F-1, which altogether define a novel protein motif, termed HNPP-box. One cl ass of splice variants contains an almost complete and highly conserved cop y of the DNA-binding high mobility group 1 protein sequence and thus repres ent novel HMG-box proteins. When expressed transiently, both major classes of Sp100 splice variant proteins localize in part to nuclear dots/PML bodie s and in addition to different nuclear domains. Furthermore, PML was occasi onally redistributed, These data indicate that alternatively spliced Sp100 proteins are expressed, differ in part in localization from Sp100, and migh t bind to chromatin via the HMG domain.