IXL, a new subunit of the mammalian Mediator complex, functions as a transcriptional suppressor

AbstractThe Mediator complex functions in eukaryotic transcription by stimulating the cooperative assembly of a pre-initiation complex (PIC) and recruitment of RNA Polymerase II (Pol II) for gene activation. The core Mediator complex is organized into head, middle, and tail modules, and in budding yeast (Saccharomyces cerevisiae), Mediator recruitment has generally been ascribed to sequence-specific activators engaging the tail module triad of Med2-Med3-Med15 at upstream activating sequences (UASs). We show that med2Δ med3Δ med15Δ yeast are viable and that Mediator lacking Med2-Med3-Med15 is associated with active promoters genome-wide. To test whether Mediator might alternatively be recruited via interactions with the PIC, we examined Mediator association genome-wide after depleting PIC components. We found that depletion of Taf1, Rpb3, and TBP profoundly affected Mediator association at active gene promoters, with TBP being critical for transit of Mediator from UAS to promoter, while Pol II and Taf1 stabilize Mediator association at proximal promoters.

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A Monoclonal Antibody to the Human Platelet Glycoprotein II b/III a Complex Induces Platelet Activation

Thrombosis and Haemostasis ◽

10.1055/s-0038-1647637 ◽

1988 ◽

Vol 60 (01) ◽

pp. 068-074 ◽

Cited By ~ 33

Author(s):

Piet W Modderman ◽

Han G Huisman ◽

Jan A van Mourik ◽

Albert E G Kr von dem Borne

Keyword(s):

Human Platelet ◽

Adenosine Diphosphate ◽

Dense Granule ◽

Platelet Glycoprotein ◽

Activated Platelets ◽

Complex Functions ◽

Slow Aggregation ◽

Irreversible Aggregation ◽

Platelet Release ◽

Aggregation Of Platelets

SummaryThe platelet glycoprotein (GP) IIb/IIIa complex functions as the receptor for fibrinogen on activated platelets. The effects of two anti-GPIIb/IIIa monoclonal antibodies on platelet function were studied. These antibodies, 6C9 and C17, recognized different epitopes, which were exclusively present on the undissociated GPIIb/IIIa complex. Whereas C17 inhibited the binding of fibrinogen to platelets and platelet aggregation induced by adenosine diphosphate (ADP) or collagen, 6C9 caused irreversible aggregation of platelets, both in the presence and absence of extracellular fibrinogen. When incubated with unstirred (nonaggregating) platelets, 6C9 induced release of alpha and dense granule-constituents as well as binding of 125I-fibrinogen to platelets. The latter was evidently mediated in part by platelet-derived ADP, since it was inhibited to a large extent by apyrase, the ADP-hydrolyzing enzyme. F(ab’)2 fragments of 6C9 did not induce platelet-release reactions but caused (slow) aggregation of platelets in the presence of extracellular fibrinogen.These results indicate that binding of an antibody to a specific site on the platelet GPIIb/IIIa complex may cause fibrinogen-mediated aggregation. The Fc part of the platelet-bound antibody appears to be involved in the induction of platelet release.

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Combinatorial Peptide Libraries for Selecting Inorganic-Binding Proteins: A Step in Molecular Biomimetics

MRS Proceedings ◽

10.1557/proc-773-n8.1 ◽

2003 ◽

Vol 773 ◽

Cited By ~ 1

Author(s):

C. Tamerler ◽

S. Dinçer ◽

D. Heidel ◽

N. Karagûler ◽

M. Sarikaya

Keyword(s):

Binding Proteins ◽

Building Blocks ◽

Molecular Engineering ◽

Inorganic Materials ◽

Combinatorial Peptide Libraries ◽

Self Assembling ◽

Complex Functions ◽

Recent Developments ◽

Specific Proteins ◽

Molecular Biomimetics

AbstractProteins, one of the building blocks in organisms, not only control the assembly in biological systems but also provide most of their complex functions. It may be possible to assemble materials for practical technological applications utilizing the unique advantages provided by proteins. Here we discuss molecular biomimetic pathways in the quest for imitating biology at the molecular scale via protein engineering. We use combinatorial biology protocols to select short polypeptides that have affinity to inorganic materials and use them in assembling novel hybrid materials. We give an overview of some of the recent developments of molecular engineering towards this goal. Inorganic surface specific proteins were identified by using cell surface and phage display technologies. Examples of metal and metal oxide specific polypeptides were represented with an emphasis on certain level of specificities. The recognition and self assembling characteristics of these inorganic-binding proteins would be employed in develeopment of hybrid multifunctional materials for novel bio- and nano-technological applications.

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