Network


Latest external collaboration on country level. Dive into details by clicking on the dots.

Hotspot


Dive into the research topics where Curt M. Horvath is active.

Publication


Featured researches published by Curt M. Horvath.


Cell | 1994

Interferon activation of the transcription factor Stat91 involves dimerization through SH2-phosphotyrosyl peptide interactions

Ke Shuai; Curt M. Horvath; Linda H.Tsai Huang; Sajjad A. Qureshi; David Cowburn; James E. Darnell

Stat91 (a 91 kd protein that acts as a signal transducer and activator of transcription) is inactive in the cytoplasm of untreated cells but is activated by phosphorylation on tyrosine in response to a number of polypeptide ligands, including interferon alpha (IFN-alpha) and IFN-gamma. We report here that the inactive Stat91 in the cytoplasm of untreated cells is a monomer and that upon IFN-gamma-induced phosphorylation it forms a stable homodimer. Only the dimer is capable of binding to a specific DNA sequence directing transcription. Through dissociation and reassociation assays, we show that dimerization of Stat91 is mediated through SH2-phosphotyrosyl peptide interactions. Dimerization involving SH2 recognition of specific phosphotyrosyl peptides may well provide a prototype for interactions among family members of STAT proteins to form different transcription complexes.


Molecular and Cellular Biology | 1999

Interacting Regions in Stat3 and c-Jun That Participate in Cooperative Transcriptional Activation

Xiaokui Zhang; Melissa H. Wrzeszczynska; Curt M. Horvath; James E. Darnell

ABSTRACT Independent but closely spaced DNA binding sites for Stat3 and c-Jun are required for maximal enhancer function in a number of genes, including the gene encoding the interleukin-6 (IL-6)-induced acute-phase response protein, α2-macroglobulin. In addition, a physical interaction of Stat3 with c-Jun, based on yeast two-hybrid interaction experiments, has been reported. Here we confirm the existence of an interaction between Stat3 and c-Jun both in vitro, with recombinant proteins, and in vivo, during transient transfection. Using fragments of both proteins, we mapped the interactive sites to the C-terminal region of c-Jun and to two regions in Stat3, within the coiled-coil domain and in a portion of the DNA binding domain distant from DNA contact sites. In transient-transfection experiments with the α2-macroglobulin enhancer, Stat3 and c-Jun cooperated to yield maximal enhancer function. Point mutations of Stat3 within the interacting domains blocked both physical interaction of Stat3 with c-Jun and their cooperation in IL-6-induced transcription directed by the α2-macroglobulin enhancer. While the amino acid sequences and the three-dimensional structures of Stat3 and Stat1 cores are very similar, fragments of Stat1 failed to bind c-Jun in vitro. Although Stat1 binds in vitro to the gamma interferon gene response (GAS) element in the α2-macroglobulin enhancer, Stat1 did not stimulate transcription, nor did Stat1 and c-Jun cooperate in driving transcription controlled by the α2-macroglobulin enhancer.


Current Opinion in Cell Biology | 1997

The state of the STATs: Recent developments in the study of signal transduction to the nucleus

Curt M. Horvath; James E. Darnell

The STATs (signal transducers and activators of transcription) are latent cytoplasmic proteins that, upon activation by cell surface bound polypeptide ligands, move to the nucleus to direct transcription. A variety of protein-protein interactions that affect the function of STATs has been recently recognized. It has become clear that the STATs are functional mosaics, or mixtures of signal transduction and transcription modules.


Molecular and Cellular Biology | 1996

Interactions between STAT and non-STAT proteins in the interferon-stimulated gene factor 3 transcription complex.

Curt M. Horvath; George R. Stark; Ian M. Kerr; James E. Darnell

The first STAT-containing transcription factor to be studied, the alpha-interferon-induced ISGF3, is composed of a Stat1:2 heterodimer and a weak DNA-binding protein, p48, that is a member of a growing family of proteins similar to the so-called interferon regulatory factor (IRF-1). The p48 and Stat1:2 heterodimer do not associate stably in the absence of DNA, but we show that amino acids approximately 150 to 250 of Stat1 and a COOH-terminal portion of p48 exhibit physical interaction, implying contact that stabilizes ISGF3. Moreover, amino acid exchanges within the Stat1 contact region diminish or abolish the functional activity of Stat1. This protein interaction domain may be important in other STAT proteins to recruit partners to multiprotein transcription factors.


Nature Genetics | 1996

Leptin activation of Stat3 in the hypothalamus of wild-type and ob/ob mice but not db/db mice.

Christian Vaisse; Jeffrey L. Halaas; Curt M. Horvath; James E. Darnell; Markus Stoffel; Jeffrey M. Friedman


Science | 1997

Defective TNF-α-Induced Apoptosis in STAT1-Null Cells Due to Low Constitutive Levels of Caspases

Aseem Kumar; Mairead Commane; Thomas W. Flickinger; Curt M. Horvath; George R. Stark


Genes & Development | 1995

A STAT protein domain that determines DNA sequence recognition suggests a novel DNA-binding domain.

Curt M. Horvath; Zilong Wen; James E. Darnell


Proceedings of the National Academy of Sciences of the United States of America | 1996

Two contact regions between Stat1 and CBP/p300 in interferon γ signaling

Jue J. Zhang; Uwe Vinkemeier; Wei Gu; Debabrata Chakravarti; Curt M. Horvath; James E. Darnell


Proceedings of the National Academy of Sciences of the United States of America | 1996

Transcriptionally active Stat1 is required for the antiproliferative effects of both interferon alpha and interferon gamma.

Jacqueline Bromberg; Curt M. Horvath; Zilong Wen; Robert D. Schreiber; James E. Darnell


Journal of Virology | 1996

The antiviral state induced by alpha interferon and gamma interferon requires transcriptionally active stat1 protein

Curt M. Horvath; James E. Darnell

Collaboration


Dive into the Curt M. Horvath's collaboration.

Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar

Zilong Wen

Hong Kong University of Science and Technology

View shared research outputs
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar

Wei Gu

Salk Institute for Biological Studies

View shared research outputs
Top Co-Authors

Avatar

Zhong Zhong

Rockefeller University

View shared research outputs
Top Co-Authors

Avatar

Uwe Vinkemeier

University of Nottingham

View shared research outputs
Researchain Logo
Decentralizing Knowledge