Su C et al. (2020) Neurochem Int "Inhibitory Potency of 4- Substituted Sampangine Derivatives toward Cu2+ mediated aggregation of amyloid -peptide, Oxidative Stress, and Inflammation in Alzheimer's Disease."

Tang H, Chen K, Li W, Su C, Chen Y

[Neurochem Int, 2020]

Cu²⁺ plays a key role in the pathogenesis of Alzheimer's disease (AD). The dysregulation of Cu²⁺ can cause neuronal damage and aggravate development of AD. Moreover, a series of 4-substituted sampangine derivatives have been investigated as inhibitors of acetylcholinesterase and -amyloid (A) aggregation for the treatment of AD in our previous studies. In the present study, we reported that one of these derivatives SD-1 was able to modulate Cu²⁺-mediated multiple pathological elements in AD. The high selectivity of SD-1 for Cu²⁺ over other biologically relevant metal ions was demonstrated by ITC. Western blotting analysis, light-scattering study, DCF-DA assay and paralysis experiment indicated that SD-1 suppressed the formation of Cu²⁺-A species, alleviated the Cu²⁺-A species induced neurotoxicity and inhibited the production of ROS catalyzed by Cu²⁺-A species in SH-SY5Y cells over-expressing the Swedish mutant form of human APP (APPsw SH-SY5Y) and A42 transgenic C elegans (CL2020). Furthermore, SD-1 inhibited the expressions of NO, iNOS, TNF-, IL-1 and IL-6 induced by Cu²⁺ in BV2 microglial cells. Collectively, these findings provided valuable insights into the design and development of potent metal-chelating agents for AD treatment.

Kurshakova M et al. (2007) Mol Cell "Evolutionarily conserved E(y)2/Sus1 protein is essential for the barrier activity of Su(Hw)-dependent insulators in Drosophila."

Georgiev P, Golovnin A, Kurshakova M, Georgieva S, Maksimenko O, Pulina M, Krasnov A

[Mol Cell, 2007]

Chromatin insulators affect interactions between promoters and enhancers/silencers and function as barriers for spreading of repressive chromatin. The Su(Hw) protein is responsible for activity of the best-studied Drosophila insulators. Here we demonstrate that an evolutionarily conserved protein, E(y)2/Sus1, is recruited to the Su(Hw) insulators via binding to the zinc-finger domain of Su(Hw). Partial inactivation of E(y)2 in a weak mutation, e(y)2(u1), impairs only the barrier, but not the enhancer-blocking, activity of the Su(Hw) insulators. Whereas neither su(Hw)(-) nor e(y)2(u1) affects fly viability, their combination proves lethal, testifying to functional interaction between Su(Hw) and E(y)2 in vivo. Apparently, different domains of Su(Hw) recruit proteins responsible for enhancer-blocking and for the barrier activity.

Guo S et al. (1994) Worm Breeder's Gazette "Identification of par-1 Gene by Injecting in vitro-transcribed anti-sense RNA"

Guo S, Kemphues KJ

[Worm Breeder's Gazette, 1994]

Identification of par-l gene by injecting in vitro- transcribed anti-sense RNA Su Guo, Kenneth Kemphues, Dept. of Genetics & Development, Cornell University, Ithaca, NY 14853

Chang-Su Lim et al. (2001) International C. elegans Meeting "Identification of two novel clk mutants"

Chang-Su Lim, Judith Campisi, Kang-Ja Lee

[International C. elegans Meeting, 2001]

It has previously been shown that mutations in the genes clk-1 , clk-2 , clk-3 , and gro-1 are highly pleiotropic, causing an increase in the average period of nematode development, a slowing of rhythmic behaviors such as defecation, swimming, and pharyngeal pumping, and a lengthening of life span. Intuitively these genes may be positioned in the same genetic pathway because mutations in any one of them give rise to similar mutant phenotypes. However, it remains possible that they might also function independently of each other. We are particularly interested in the life span extension conferred by clk mutants. To begin to understand how clk genes function in life span regulation, we performed five independent EMS mutagenesis experiments, screening 20, 000 mutagenized genomes in total. We identified two novel clk mutants. Both mutants complement each other, or the four known clk mutants, clk-1 , clk-2 , clk-3 , and gro-1 . Currently, we are characterizing the phenotypes of the clk-4 and clk-5 mutants.

Tanaka YU et al. (1995) DNA Res "Developmental expression pattern of the Caenorhabditis elegans homologue of the Drosophila suppressor of forked gene."

Sakamoto H, Matsuo M, Ohta A, Tanaka YU

[DNA Res, 1995]

We cloned and sequenced the cDNA which encodes the Caenorhabditis elegans homologue (suf-1) of the Drosophila suppressor of forked (su(f)) gene product. The amino acid sequence deduced from the suf-1 cDNA shares extensive similarity with the su(f) and the human 77K subunit of the CstF, including the proline residues near the carboxy-terminus. Developmental Northern blot analysis showed that a 2.6-kb suf-1 transcript was expressed constitutively from L1 to young adult stages, suggesting it has a housekeeping function in vivo. Furthermore, this idea is consistent with the recent proposition that su(f) homologues play an essential role as a subunit of the cleavage stimulation factor (CstF) during polyadenylation of mRNA precursors.

Alexandre Neves et al. (2006) Development & Evolution Meeting "A Notch-GATA Transcription Code for Endoderm-Specific Gene Activation in C.elegans"

James Priess, Alexandre Neves

[Development & Evolution Meeting, 2006]

Several Notch interactions occur in rapid succession during early C.elegans embryogenesis, each resulting in a distinct fate. We have previously shown that ref-1, a gene distantly related to Drosophila E(spl), is a direct Notch target in all these interactions. We show here that ref-1 expression is controlled by multiple, Notch-dependent enhancers that are specific for each interaction. We have identified a 150bp enhancer that is specific to Notch interactions in the endoderm, and found similar enhancers with the same activity in C.briggsae and C.remanei. The endoderm enhancer contains multiple, conserved binding sites for LAG-1/Su(H) and GATA transcription factors. We demonstrate that all LAG-1/Su(H) and GATA sites are required for full activity of this enhancer. We provide evidence that a GATA transcription factor called ELT-2 is a cooperative factor for Notch in the endoderm. Ectopic expression of ELT-2 in non-endodermal lineages caused activation of the endoderm enhancer only in Notch-signaled cells, suggesting that the presence of the cooperative factor dictates in which Notch interaction a Notch-dependent enhancer becomes responsive in vivo. Previous studies in Drosophila showed that synergy between Su(H) and the bHLH transcription factor Daughterless requires a specific configuration of Su(H) sites, known as a Su(H) paired site, SPS. The endoderm enhancer contains a putative SPS. However, we find that Notch-GATA synergy does not require a SPS, and instead requires a non-SPS configuration of oriented LAG-1/Su(H) sites. Thus, it appears that that each configuration couples Notch signaling with a specific class of transcription factor.

Su M-W et al. (1993) International C. elegans Meeting "Spatial regulation of unc-5 expression."

Scott IM, Su M-W, Zhou YW, Hedgecock EM, Culotti JG

[International C. elegans Meeting, 1993]

Su M-W et al. (1995) International C. elegans Meeting "UNC-5 INDUCES TURNING OF THE DISTAL TIP CELLS"

Kramer JM, Zhou YW, Su M-W, Hedgecock EM, Culotti JG

[International C. elegans Meeting, 1995]

Each distal tip cell (DTC) migration comprises 3 sequential phases: a longitudinal phase followed by a ventral to dorsal phase followed by a retrograde longitudinal phase. The male linker cell exhibits a similar pattern of migratory phases. We have examined the expression of lacZ reporters from the unc-5 promoter to determine what role UNC-5 expression might play in the first right angle turn of these cells. unc-5-lacZ first expresses in the DTCs precisely at the time of their first turn in wild type animals (1993 Mtg Abst., p.429). unc-5-lacZ expression in the male linker cell and in mutants affecting DTC migrations (e.g., unc-5, unc-6, unc-40, mig-7, & mig-8) or position (e.g., dig-1, & mig-4) further extend the correlation between expression and turning, suggesting that UNC-5 expression may induce the turn. To test this hypothesis, we expressed UNC-5 precociously in the DTCs under the control of the emb-9 promoter. Preliminary results suggest that in a fraction of emb-9-unc-5 transgenic animals the DTCs are induced to turn precociously.

Su M-W et al. (1993) International C. elegans Meeting "Temporal regulation of unc-5 expression in distal tip cells."

Hedgecock EM, Su M-W, Zhou YW, Culotti JG

[International C. elegans Meeting, 1993]

Ketel, CS et al. (2005) Mol Cell Biol "Subunit contributions to histone methyltransferase activities of fly and worm polycomb group complexes."

Vargas, ML, Andersen, EF, Strome, S, Ketel, CS, Suh, J, Simon, JA

[Mol Cell Biol, 2005]

The ESC-E(Z) complex of Drosophila melanogaster Polycomb group (PcG) repressors is a histone H3 methyltransferase (HMTase). This complex silences fly Hox genes, and related HMTases control germ line development in worms, flowering in plants, and X inactivation in mammals. The fly complex contains a catalytic SET domain subunit, E(Z), plus three noncatalytic subunits, SU(Z)12, ESC, and NURF-55. The four-subunit complex is > 1,000-fold more active than E(Z) alone. Here we show that ESC and SU(Z)12 play key roles in potentiating E(Z) HMTase activity. We also show that loss of ESC disrupts global methylation of histone H3-lysine 27 in fly embryos. Subunit mutations identify domains required for catalytic activity and/or binding to specific partners. We describe missense mutations in surface loops of ESC, in the CXC domain of E(Z), and in the conserved VEFS domain of SU(Z)12, which each disrupt HMTase activity but preserve complex assembly. Thus, the E(Z) SET domain requires multiple partner inputs to produce active HMTase. We also find that a recombinant worm complex containing the E(Z) homolog, MES-2, has robust HMTase activity, which depends upon both MES-6, an ESC homolog, and MES-3, a pioneer protein. Thus, although the fly and mammalian PcG complexes absolutely require SU(Z)12, the worm complex generates HMTase activity from a distinct partner set.