scholarly journals Interaction of the τ2 Transcriptional Activation Domain of Glucocorticoid Receptor with a Novel Steroid Receptor Coactivator, Hic-5, Which Localizes to Both Focal Adhesions and the Nuclear Matrix

2000 ◽  
Vol 11 (6) ◽  
pp. 2007-2018 ◽  
Author(s):  
Lan Yang ◽  
Jennifer Guerrero ◽  
Heng Hong ◽  
Donald B. DeFranco ◽  
Michael R. Stallcup
Keyword(s):  
Estrogen Receptor ◽  
Glucocorticoid Receptor ◽  
Nuclear Matrix ◽  
Transcriptional Activation ◽  
Steroid Receptors ◽  
Focal Adhesions ◽  
Steroid Receptor ◽  
Terminal Region ◽  
Activation Domain ◽  
Transcriptional Activation Domain

Hic-5 (hydrogen peroxide–inducible clone-5) is a focal adhesion protein that is involved in cellular senescence. In the present study, a yeast two-hybrid screen identified Hic-5 as a protein that interacts with a region of the glucocorticoid receptor that includes a nuclear matrix–targeting signal and the τ2 transcriptional activation domain. In transiently transfected mammalian cells, overexpression of Hic-5 potentiated the activation of reporter genes by all steroid receptors, excluding the estrogen receptor. The activity of the estrogen receptor and the thyroid hormone receptor was stimulated by Hic-5 in the presence but not in the absence of coexpressed coactivator GRIP1. In biochemical fractionations and indirect immunofluorescence assays, a fraction of endogenous Hic-5 in REF-52 cells and transiently expressed Hic-5 in Cos-1 cells was associated with the nuclear matrix. The C-terminal region of Hic-5, which contains seven zinc fingers arranged in four LIM domains, was required for interaction with focal adhesions, the nuclear matrix, steroid receptors, and the τ2 domain of glucocorticoid receptor. The N-terminal region of Hic-5 possesses a transcriptional activation domain and was essential for the coactivator activity of Hic-5. Given the coexisting cytoplasmic and nuclear distributions of Hic-5 and its role in steroid receptor–mediated transcriptional activation, it is proposed that Hic-5 might transmit signals that emanate at cell attachment sites and regulate transcription factors, such as steroid receptors.

scholarly journals Complex Transcriptional Effects of p63 Isoforms: Identification of Novel Activation and Repression Domains†

2002 ◽  
Vol 22 (24) ◽  
pp. 8659-8668 ◽  
Author(s):  
Pamela Ghioni ◽  
Fabrizio Bolognese ◽  
Pascal H. G. Duijf ◽  
Hans van Bokhoven ◽  
Roberto Mantovani ◽  
...  
Keyword(s):  
Transcriptional Activation ◽  
Transcriptional Repression ◽  
Ectodermal Dysplasia ◽  
Terminal Region ◽  
Single Amino Acid ◽  
Activation Domain ◽  
Transcriptional Activation Domain ◽  
Sam Domain ◽  
Frameshift Mutant ◽  
P63 Isoforms

ABSTRACT p63 is a transcription factor structurally related to the p53 tumor suppressor. The C-terminal region differs from p53's in that it contains a sterile alpha motif (SAM) domain and is subject to multiple alternative splicings. The N-terminal region is present in the transactivation (TA) and ΔN configurations, with the latter lacking the transcriptional activation domain 1. Single amino acid substitutions and frameshift mutations of p63 cause the human ankyloblepharon ectodermal dysplasia clefting (AEC) or ectrodactyly ectodermal dysplasia and facial clefting (EEC) syndromes. We have systematically compared the activities of the wild-type p63 isoforms and of the natural mutants in activation and repression assays on three promoters modulated by p53. We found that p63 proteins with an altered SAM domain or no SAM domain—the β isoforms, the EEC frameshift mutant, and the missense AEC mutations—all showed a distinctly higher level of activation of the MDM2 promoter and decreased repression on the HSP70 promoter. Fusion of SAM to the GAL4 DNA-binding domain repressed a heterologous promoter. A second activation domain, TA2, corresponding to exons 11 to 12, was uncovered by comparing the activation of ΔN isoforms on natural promoters and in GAL4 fusion systems. In colony formation assays, the AEC mutants, but not the EEC frameshift, were consistently less efficient in suppressing growth, in both the TA version and the ΔN version, with respect to their p63α counterparts. These data highlight the modularity of p63, identifying the SAM domain as a dominant transcriptional repression module and indicating that the AEC and EEC frameshift mutants are characterized by a subversion of the p63 transcriptional potential.

scholarly journals Fos and jun cooperate in transcriptional regulation via heterologous activation domains.

1990 ◽  
Vol 10 (10) ◽  
pp. 5532-5535 ◽  
Author(s):  
C Abate ◽  
D Luk ◽  
E Gagne ◽  
R G Roeder ◽  
T Curran
Keyword(s):  
Gene Expression ◽  
Transcriptional Activation ◽  
Transcriptional Activity ◽  
Regulation Of Gene Expression ◽  
Negative Influence ◽  
Activation Domain ◽  
Activation Domains ◽  
Transcriptional Activation Domain ◽  
Transcriptional Stimulation

The products of c-fos and c-jun (Fos and Jun) function in gene regulation by interacting with the AP-1 binding site. Here we have examined the contribution of Fos and Jun toward transcriptional activity by using Fos and Jun polypeptides purified from Escherichia coli. Fos contained a transcriptional activation domain as well as a region which exerted a negative influence on transcriptional activity in vitro. Moreover, distinct activation domains in both Fos and Jun functioned cooperatively in transcriptional stimulation. Thus, regulation of gene expression by Fos and Jun results from an integration of several functional domains in a bimolecular complex.

scholarly journals The ubiquitin-proteasome pathway is required for the function of the viral VP16 transcriptional activation domain

FEBS Letters ◽  
2003 ◽  
Vol 556 (1-3) ◽  
pp. 19-25 ◽  
Author(s):  
Qianzheng Zhu ◽  
Jihong Yao ◽  
Gulzar Wani ◽  
Jianming Chen ◽  
Qi-En Wang ◽  
...  
Keyword(s):  
Transcriptional Activation ◽  
Activation Domain ◽  
Transcriptional Activation Domain ◽  
Ubiquitin Proteasome Pathway ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway

Transcriptional Activation Domain of Human BTEB2, A GC Box-Binding Factor

1997 ◽  
Vol 121 (2) ◽  
pp. 389-396 ◽  
Author(s):  
S. Kojima ◽  
A. Kobayashi ◽  
O. Gotoh ◽  
Y. Ohkuma ◽  
Y. Fujii-Kuriyama ◽  
...  
Keyword(s):  
Transcriptional Activation ◽  
Activation Domain ◽  
Transcriptional Activation Domain ◽  
Binding Factor ◽  
Gc Box

Frazzled/Dcc acts independently of Netrin to promote germline survival during Drosophila oogenesis

Development ◽  
2021 ◽  
Vol 148 (24) ◽  
Author(s):  
Samantha A. Russell ◽  
Kaitlin M. Laws ◽  
Greg J. Bashaw
Keyword(s):  
Cell Death ◽  
Axon Guidance ◽  
Transcriptional Activation ◽  
Nutrient Sensing ◽  
Activation Domain ◽  
Transcriptional Activation Domain ◽  
Egg Chambers ◽  
Death Effector ◽  
Female Germline

ABSTRACT The Netrin receptor Frazzled/Dcc (Fra in Drosophila) functions in diverse tissue contexts to regulate cell migration, axon guidance and cell survival. Fra signals in response to Netrin to regulate the cytoskeleton and also acts independently of Netrin to directly regulate transcription during axon guidance in Drosophila. In other contexts, Dcc acts as a tumor suppressor by directly promoting apoptosis. In this study, we report that Fra is required in the Drosophila female germline for the progression of egg chambers through mid-oogenesis. Loss of Fra in the germline, but not the somatic cells of the ovary, results in the degeneration of egg chambers. Although a failure in nutrient sensing and disruptions in egg chamber polarity can result in degeneration at mid-oogenesis, these factors do not appear to be affected in fra germline mutants. However, similar to the degeneration that occurs in those contexts, the cell death effector Dcp-1 is activated in fra germline mutants. The function of Fra in the female germline is independent of Netrin and requires the transcriptional activation domain of Fra. In contrast to the role of Dcc in promoting cell death, our observations reveal a role for Fra in regulating germline survival by inhibiting apoptosis.

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