We have previously shown that the mouse heterochromatin protein 1 homologue M31 interacts dynamically with the nuclear envelope. Using quantitative in vitro assays, we now demonstrate that this interaction is potently inhibited by soluble factors present in mitotic and interphase cytosol. As indicated by depletion and orderof-addition experiments, the inhibitory activity co-isolates with a 55-kDa protein, which binds avidly to the nuclear envelope and presumably blocks M31-binding sites. Purification of this protein and microsequencing of tryptic peptides identify it as ␣2/6:2-tubulin. Consistent with this observation, bona fide tubulin, isolated from rat brain and maintained in a nonpolymerized state, abolishes binding of M31 to the nuclear envelope and aborts M31-mediated nuclear envelope reassembly in an in vitro system. These observations provide a new example of "moonlighting," a process whereby multimeric proteins switch function when their aggregation state or localization is altered. Heterochromatin protein 1 (HP1)1 represents the founding member of a large protein family, which includes the Polycomb group and other gene regulators (for recent reviews see Refs. 1 and 2). This molecule possesses a dimeric, quasi-symmetrical structure and contains two sequence-related and similarly folded domains: the N-terminal chromodomain (3, 4), and the C-terminal chromo shadow domain (5). These two domains consist of anti-parallel, three-stranded -sheets packed against one or two ␣-helices and are separated from one another by a flexible hinge region. Dimerization of HP1 involves intermolecular interactions between chromo shadow domains that tether two polypeptide chains at their C-terminal ends but leave the chromodomains unconstrained (6, 7).A single HP1 species was originally identified in Drosophila melanogaster (8). However, subsequent studies have revealed multiple variants of this protein in higher eukaryotes. Mammalian HP1 includes three distinct isotypes termed hHP1␣, , and ␥ in humans and mHP1␣, M31, and M32 in mice (3, 9 -11). Although these proteins are structurally similar, they are distributed in different territories of the cell nucleus (12-15).HP1 binds to several chromatin-remodeling factors and transcriptional regulators. Among these are CAF-1, BRG1/SNF2, and the transcriptional intermediary factors ␣ and  (7, 10, 15, 16). Physical or spatial associations between HP1 and elements of the origin recognition complex, actin-related proteins (Arp4), and SET or chromodomain-containing proteins, such as Su(var)3-9 and Su(var)3-7 have also been described (14,(17)(18)(19). Finally, interactions with the centromeric protein inner centromere protein, the nuclear autoantigen SP100, and the inner nuclear membrane protein LBR have been reported recently (10, 11, 20 -23).The interactions between HP1 proteins and elements of the nuclear envelope are particularly intriguing. First, peripheral heterochromatin is in physical contact with the inner nuclear membrane during interphase and could be directly linked to ...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.