Oligomerization-dependent Association of the SAM Domains from Schizosaccharomyces pombe Byr2 and Ste4

Ramachander, Ranjini; Kim, Chongwoo A.; Phillips, Martin; Mackereth, Cameron D.; Thanos, Christopher D.; McIntosh, Lawrence P.; Bowie, James U.

doi:10.1074/jbc.m207273200

Cited by 43 publications

(43 citation statements)

References 46 publications

(47 reference statements)

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“…These domains were subsequently found in other proteins involved in the regulation of numerous developmental processes among eukaryotes, suggesting that SAM domains were evolutionarily conserved. These domains tend to oligomerize, forming either homooligomers or heterooligomers, sometimes with non-1:1 stoichiometries, and their interactions with proteins lacking SAM domains have also been described (44). Moreover, some SAM domains are known to self-associate using multiple binding protein surfaces to generate polymeric structures (45).…”

Section: Discussionmentioning

confidence: 99%

Binding of the C-terminal Sterile α Motif (SAM) Domain of Human p73 to Lipid Membranes

Barrera

Poveda

González-Ros

et al. 2003

Journal of Biological Chemistry

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The ␣ splice variant of p73 (p73␣), a homologue of the tumor suppressor p53, has close to its C terminus a sterile ␣ motif (SAM), SAMp73, that is thought to be involved in protein-protein interactions. Here, we report the lipid binding properties of this domain. Binding was assayed against zwitterionic (phosphatidylcholine) and anionic (phosphatidic acid) lipids and was studied by different biophysical techniques, namely, circular dichroism and fluorescence spectroscopies and differential scanning calorimetry. These techniques unambiguously indicate that SAMp73 binds to lipids. The binding involves protein surface attachment and partial membrane penetration, accompanied by changes in SAMp73 structure.p73 and p63 are members of the p53 gene family (1, 2). As the tumor suppressor p53, p73 and p63 are also transcription factors that contain an N-terminal transactivation domain, a sequence-specific DNA-binding domain, and an oligomerization domain with a high sequence homology to the corresponding domains of p53. For instance, p73 shares 63% identity with the DNA-binding region of p53 (including the conservation of all DNA-binding residues), 38% identity with the tetramerization domain, and 29% with the transactivation domain. Furthermore, p73 and p63 share a relative functional homology with p53, because they can both activate transcription from p53-responsive genes, stop the cell cycle, and induce apoptosis when overexpressed. Moreover, p73 is positively regulated in p53-

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Section: Discussionmentioning

confidence: 99%

Binding of the C-terminal Sterile α Motif (SAM) Domain of Human p73 to Lipid Membranes

Barrera

Poveda

González-Ros

et al. 2003

Journal of Biological Chemistry

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“…Unlike many other protein-protein interaction modules that have a common, well defined function such as SH2 domains, SAM domains can play diverse roles. To date, SAM domains are known to form homo-and heterooligomers that can be polymeric (7)(8)(9) or have a discrete oligomeric state (10), they can bind to other proteins (11,12), and they can even bind RNA (13,14).…”

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confidence: 99%

Structural Organization of a Sex-comb-on-midleg/Polyhomeotic Copolymer

Kim¹,

Sawaya

Cascio

et al. 2005

Journal of Biological Chemistry

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103

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The polycomb group proteins are required for the stable maintenance of gene repression patterns established during development. They function as part of large multiprotein complexes created via a multitude of proteinprotein interaction domains. Here we examine the interaction between the SAM domains of the polycomb group proteins polyhomeotic (Ph) and Sex-comb-on-midleg (Scm). Previously we showed that Ph-SAM polymerizes as a helical structure. We find that Scm-SAM also polymerizes, and a crystal structure reveals an architecture similar to the Ph-SAM polymer. These results suggest that Ph-SAM and Scm-SAM form a copolymer. Binding affinity measurements between Scm-SAM and Ph-SAM subunits in different orientations indicate a preference for the formation of a single junction copolymer. To provide a model of the copolymer, we determined the structure of the Ph-SAM/Scm-SAM junction. Similar binding modes are observed in both homo-and heterocomplex formation with minimal change in helix axis direction at the polymer joint. The copolymer model suggests that polymeric Scm complexes could extend beyond the local domains of polymeric Ph complexes on chromatin, possibly playing a role in long range repression.The PcG 1 proteins form large multiprotein complexes that repress transcription over long distances and maintain repressed states in a stable and heritable manner during embryogenesis, development, and into adulthood (1, 2). PcG mutations result in both developmental defects and cancer (3-5). The formation of such large complex structures requires the precise organization of many proteins of the PcG. Indeed, protein-protein interaction domains are the most common functional motifs that have been identified in the PcG family. Nevertheless, few of these domains have been characterized in detail, and the structural architecture of the resultant protein complexes is largely unknown.One protein-protein interaction domain present in the PcG family is the SAM (sterile alpha motif) domain (often called SPM in PcG literature) found in polyhomeotic (Ph) and Sexcomb-on-midleg (Scm). SAM domains are small, helical protein modules found in proteins with diverse functional roles ranging from receptor tyrosine kinases to transcription factors (6). Unlike many other protein-protein interaction modules that have a common, well defined function such as SH2 domains, SAM domains can play diverse roles. To date, SAM domains are known to form homo-and heterooligomers that can be polymeric (7-9) or have a discrete oligomeric state (10), they can bind to other proteins (11, 12), and they can even bind RNA (13,14).Ph and Scm proteins co-localize on polytene chromosomes (15) and can interact via their SAM domains (15-17). The interaction between Ph and Scm appears to be complex. In addition to binding to each other, the SAM domains of Ph and Scm can also self-associate and thus exist in a higher oligomeric state of their own (8,15,16). Although they appear to work at the same sites, isolation of the soluble form of one PcG protein complex, PR...

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“…In C. elegans, Cnk-1 acts downstream of Raf dephosphorylation, but upstream of the activating phosphorylation events (Rocheleau et al 2005). SAM domains have been shown to mediate homo-or heterooligomerization in both nuclear and membrane proteins (Stapleton et al 1999;Kim et al 2001Kim et al , 2002Ramachander et al 2002), suggesting that the function of the SAM domain of Cnk might be to interact with another SAM domain protein; however, such a partner has not yet been identified.…”

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confidence: 99%

The novel SAM domain protein Aveugle is required for Raf activation in the Drosophila EGF receptor signaling pathway

Roignant¹,

Hamel²,

Janody³

et al. 2006

Genes Dev.

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Activation of the Raf kinase by GTP-bound Ras is a poorly understood step in receptor tyrosine kinase signaling pathways. One such pathway, the epidermal growth factor receptor (EGFR) pathway, is critical for cell differentiation, survival, and cell cycle regulation in many systems, including the Drosophila eye. We have identified a mutation in a novel gene, aveugle, based on its requirement for normal photoreceptor differentiation. The phenotypes of aveugle mutant cells in the eye and wing imaginal discs resemble those caused by reduction of EGFR pathway function. We show that aveugle is required between ras and raf for EGFR signaling in the eye and for mitogen-activated protein kinase phosphorylation in cell culture. aveugle encodes a small protein with a sterile ␣ motif (SAM) domain that can physically interact with the scaffold protein connector enhancer of Ksr (Cnk). We propose that Aveugle acts together with Cnk to promote Raf activation, perhaps by recruiting an activating kinase. Many receptor tyrosine kinases (RTKs), including the epidermal growth factor receptor (EGFR) and fibroblast growth factor receptor (FGFR), signal through the Ras/ mitogen-activated protein kinase (MAPK) pathway (Nishida and Gotoh 1993). These receptors have important developmental functions and are also misregulated in a variety of cancers (Holbro and Hynes 2004), making it critical to understand their signaling mechanism. Genetic screens in Drosophila and Caenorhabditis elegans, coupled with biochemical analysis in cultured cells, have allowed the identification of numerous Ras/MAPK pathway components (Rubin et al. 1997;Moghal and Sternberg 2003).The Drosophila eye is a particularly useful system for genetic analysis of the EGFR pathway, which has welldefined functions in photoreceptor development (Freeman 1997;Halfar et al. 2001;Yang and Baker 2003). As the morphogen Hedgehog (Hh) drives progression of the morphogenetic furrow across the eye disc, it induces the expression of the transcription factor Atonal, which specifies the first photoreceptor to differentiate in each cluster, R8 (Jarman et al. 1995;Dominguez 1999). Once the R8 photoreceptor has been specified, it sequentially recruits additional photoreceptors, cone cells, and pigment cells from the surrounding pool of undifferentiated cells. The signal for this recruitment is the EGFR ligand Spitz (Spi), which is secreted by R8 and subsequently by other photoreceptors as they differentiate (Freeman 1996). Production of the downstream feedback inhibitor Argos (Aos), which binds to Spi and blocks its binding to the receptor (Klein et al. 2004), restricts the response to Spi to a small number of cells, allowing the stepwise recruitment of ommatidial cell types (Freeman 1997). A second RTK, Sevenless, also contributes to R7 differentiation (Freeman 1996). The precursors of the R2, R5, R3, and R4 photoreceptors remain arrested in the G1 phase of the cell cycle after leaving the morphogenetic furrow. This arrest also requires EGFR signaling, but occurs at a lower threshold tha...

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Oligomerization-dependent Association of the SAM Domains from Schizosaccharomyces pombe Byr2 and Ste4

Cited by 43 publications

References 46 publications

Binding of the C-terminal Sterile α Motif (SAM) Domain of Human p73 to Lipid Membranes

Binding of the C-terminal Sterile α Motif (SAM) Domain of Human p73 to Lipid Membranes

Structural Organization of a Sex-comb-on-midleg/Polyhomeotic Copolymer

The novel SAM domain protein Aveugle is required for Raf activation in the Drosophila EGF receptor signaling pathway

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