In many animals, establishment of the germ line depends on segregation of a specialized cytoplasm, or 'germ plasm', to a small number of germline precursor cells during early embryogenesis. Germ plasm asymmetry involves targeting of RNAs and proteins to a specific region of the oocyte and/or embryo. Here we demonstrate that germ plasm asymmetry also depends on degradation of germline proteins in non-germline (somatic) cells. We show that five CCCH finger proteins, components of the Caenorhabditis elegans germ plasm, are targeted for degradation by the novel CCCH-finger-binding protein ZIF-1. ZIF-1 is a SOCS-box protein that interacts with the E3 ubiquitin ligase subunit elongin C. Elongin C, the cullin CUL-2, the ring finger protein RBX-1 and the E2 ubiquitin conjugation enzyme UBC5 (also known as LET-70) are all required in vivo for CCCH finger protein degradation. Degradation is activated in somatic cells by the redundant CCCH finger proteins MEX-5 and MEX-6, which are counteracted in the germ line by the PAR-1 kinase. We propose that segregation of the germ plasm involves both stabilization of germline proteins in the germ line and cullin-dependent degradation in the soma.
The mammalian hairless (hr) gene plays a critical role in the maintenance of hair growth. Although the hr gene has been identified, the biochemical function of its encoded protein (Hr) has remained obscure. Here, we show that Hr functions as a transcriptional corepressor for thyroid hormone receptors (TRs). We find that two independent regions of Hr mediate TR binding and that interaction requires a cluster of hydrophobic residues similar to the binding motifs proposed for nuclear receptor corepressors (N-CoR and SMRT). Similarly, we show that Hr binds to the same region of TR as known corepressors. We show that Hr interacts with histone deacetylases (HDACs) and is localized to matrix-associated deacetylase (MAD) bodies, indicating that the mechanism of Hr-mediated repression is likely through associated HDAC activity. Thus, Hr is a component of the corepressor machinery, and despite its lack of sequence identity with previously described corepressors, its mode of action is remarkably conserved. On the basis of its thyroid hormone-inducible and tissue-and developmental-specific expression, Hr likely defines a new class of nuclear receptor corepressors that serve a more specialized role than ubiquitous corepressors. The discovery that Hr is a corepressor provides a molecular basis for specific hair loss syndromes in both humans and mice.
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.