Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P51532 (transcriptional activator)
 6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Proteins containing high-mobility group (HMG) domains are segregated into two major groups. Members of one group are identified by the presence of more than one HMG domain that binds to DNA without sequence specificity, and they are usually ubiquitously expressed. In contrast, members of the other group possess a single HMG domain with high affinity to specific DNA sequences. Generally, members of the second group resemble classic tissue-specific transcriptional regulators. In contrast, Smarce1/BAF-57 is a ubiquitously expressed, novel protein with a single HMG domain that displays nonspecific DNA-binding characteristics. Additionally, as a core subunit of the mammalian SWI/SNF-like transcriptional activator complex, Smarce1/BAF-57 is also the first member of the HMG protein family that was reported to contain a kinesin-like coiled-coil (KLCC) domain. Here we report the cloning, as well as the chromosomal and phylogenetic analysis, of a novel mammalian protein that is structurally related to Smarce1, termed Smarce1-related (Smarce1r). The unique arrangement of an HMG with a KLCC domain shared with Smarce1/BAF-57 suggests a similar, albeit still unknown, function in chromatin assembly as part of a mammalian SWI/SNF-like complex. The linkage of a single nonspecific DNA-binding HMG domain with a KLCC domain makes both proteins the founding members of a third group of HMG proteins.
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PMID:Cloning, chromosomal location, and expression analysis of murine Smarce1-related, a new member of the high-mobility 365 group gene family. 1048 8

ACT is a LIM-only protein expressed exclusively in round spermatids, where it cooperates with transcriptional activator CREM in regulating various postmeiotic genes. Targeted inactivation of CREM leads to a complete block of mouse spermiogenesis. We sought to identify the regulatory steps controlling the functional interplay between CREM and ACT. We found that ACT selectively associates with KIF17b, a kinesin highly expressed in male germ cells. The ACT-KIF17b interaction is restricted to specific stages of spermatogenesis and directly determines the intracellular localization of ACT. Sensitivity to leptomycin B indicates that KIF17b can be actively exported from the nucleus through the Crm1 receptor. Thus, a kinesin directly controls the activity of a transcriptional coactivator by a tight regulation of its intracellular localization.
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PMID:CREM-dependent transcription in male germ cells controlled by a kinesin. 1249 14

The transcriptional program orchestrated by Hedgehog signaling depends on the Gli family of transcription factors. Gli proteins can be converted to either transcriptional activators or truncated transcriptional repressors. We show that the interaction between Gli3 and Suppressor of Fused (Sufu) regulates the formation of either repressor or activator forms of Gli3. In the absence of signaling, Sufu restrains Gli3 in the cytoplasm, promoting its processing into a repressor. Initiation of signaling triggers the dissociation of Sufu from Gli3. This event prevents formation of the repressor and instead allows Gli3 to enter the nucleus, where it is converted into a labile, differentially phosphorylated transcriptional activator. This key dissociation event depends on Kif3a, a kinesin motor required for the function of primary cilia. We propose that the Sufu-Gli3 interaction is a major control point in the Hedgehog pathway, a pathway that plays important roles in both development and cancer.
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PMID:The output of Hedgehog signaling is controlled by the dynamic association between Suppressor of Fused and the Gli proteins. 2036 Mar 84

Extracellular Hedgehog (Hh) proteins alter cellular behaviours from flies to man by regulating the activities of Gli/Ci family transcription factors. A major component of this response in Drosophila is the inhibition of proteolytic processing of the latent transcriptional activator Ci-155 to a shorter Ci-75 repressor form. Processing is thought to rely on binding of the kinesin-family protein Cos2 directly to Ci-155 domains known as CDN and CORD, allowing Cos2-associated protein kinases to phosphorylate Ci-155 efficiently and create a binding site for an E3 ubiquitin ligase complex. Here we show that the last three zinc fingers of Ci-155 also bind Cos2 in vitro and that the zinc finger region, rather than the CDN domain, functions redundantly with the CORD domain to promote Hh-regulated Ci-155 proteolysis in wing discs. We also find evidence for a unique function of Cos2 binding to CORD. Cos2 binding to CORD, but not to other regions of Ci, is potentiated by nucleotides and abrogated by the nucleotide binding variant Cos2 S182N. Removal of the CORD region alone enhances processing under a variety of conditions. Most strikingly, CORD region deletion allows Cos2 S182N to stimulate efficient Ci processing. We deduce that the CORD region has a second function distinct from Cos2 binding that inhibits Ci processing, and that Cos2 binding to CORD relieves this inhibition. We suggest that this regulatory activity of Cos2 depends on a specific nucleotide-bound conformation that may be regulated by Hh.
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PMID:Costal 2 interactions with Cubitus interruptus (Ci) underlying Hedgehog-regulated Ci processing. 2085 Apr 29