A Novel Protein Specifically Interacting with Homer2 Regulates Ubiquitin-Proteasome Systems

Abstract

Homer family proteins are encoded by three genes, homer1, 2 and 3. Most of these proteins are expressed constitutively in nervous systems and accumulated in postsynaptic regions. However, the functional significance of these proteins, especially the significance of the distinction among the proteins encoded by homer1, 2 and 3, is still obscure. In the present study, we isolated a cDNA clone encoding a novel protein by two-hybrid system screening using the C-terminal half of Homer2b as the bait. This protein, termed 2B28, has 297 amino acid residues and contains three major domains: a UBA domain, a coiled-coil region, and a UBX domain. When expressed in HEK293T cells, 2B28 showed colocalization with uniquitin and enhanced the expression levels of IkappaB or Homer1a proteins, which are known to be degraded by proteasomes, indicating that 2B28 is involved in ubiquitin-proteasome functions. 2B28 specifically interacted and colocalized with Homer2 proteins, but not with Homer1 proteins. So far, we have identified no counterpart of 2B28 for Homer1 experimentally or in the protein databases. These results suggest that the specific interaction of 2B28 with Homer2 may play a role in regulation of protein degradation by ubiquitin-proteasome systems and that this function may be specific to Homer2 proteins among Homer family proteins.

Tetrameric Hub Structure of Postsynaptic Scaffolding Protein Homer

“…This extra length of coiled-coil domain in Homer increases the complexity of the protein and affects the hydrodynamic nature of the protein. Also, the coiled-coil domain has been shown to interact with Rho family small G-proteins (Shiraishi et al, 1999), a SNARE family protein syntaxin-13 (Minakami et al, 2000), and a ubiquitin pathway protein 2B28 (Ishibashi et al, 2005); such interactions might also contribute to our observation. Additional multimerization of the tetramer may also be a potential mechanism for spine localization.…”

UBXN1 Interferes with Rig-I-like Receptor-Mediated Antiviral Immune Response by Targeting MAVS

“…To determine whether the immunoregulatory function of UBXN1 is conserved across species, we generated an expression plasmid encoding the mouse Ubxn1 cDNA. The amino acid sequences of UBXN1 are highly homologous between human, mouse, and rat (Ishibashi et al, 2005). Both human and mouse UBXN1 proteins are 297 amino acids and share 91.3% homology, implying conserved function (Figures S4A and S4B).…”

UBXD Proteins: A Family of Proteins with Diverse Functions in Cancer

“…The presence of diverse domains and their different combinations in the UBXD family allow these proteins to have different functional properties. These differences allow them to bind to a selected set of partners and cross-talk with different protein complexes in a subcellular localization-dependent manner [4,7,8,9,10,11,12,13,14,15,16]. Furthermore, the presence of other ubiquitin-related motifs besides the UBX domain enable UBXD proteins to exert non-redundant functions in the ubiquitin-proteasome pathway [17,18].…”