Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The activity of the glucocorticoid receptor (GR) is modulated by posttranslational modifications, protein stability, and cofactor recruitment. In this report, we investigated the role of the stress-responsive activator of p300/tetratricopeptide repeat domain 5 (TTC5), in the regulation of the GR. TTC5 is a member of the TTC family of proteins and has previously been shown to participate in the cellular response to DNA damage and heat shock. Here, we demonstrate that TTC5 is an important cofactor for the nuclear hormone receptors GR and estrogen receptor. GR and TTC5 interact through multiple tetratricopeptide repeat and LXXLL motifs. TTC5 stabilizes GR and increases its half-life, through a proteasome-dependent process and by inhibiting the actions of the ubiquitin ligase murine double minute 2. Cellular stress, including DNA damage, proteasome inhibition, and heat shock, modulates the interaction pattern of GR/TTC5, thereby altering GR stability and transcriptional activity. Furthermore, GR transcriptional activity is regulated by TTC5 in both a positive and negative fashion under DNA damage conditions in a target gene-specific way. In this report we provide evidence supporting the notion that TTC5 is a novel cofactor regulating GR function in a stress-dependent manner.
Mol Endocrinol 2011 Jan
PMID:Regulation of glucocorticoid receptor activity by a stress responsive transcriptional cofactor. 2114 50

The transcription factor p53 and AP-1 play an important role in cellular proliferation, transformation and death. In this study, we investigated the role of a novel human gene, TTC5 (tetratricopeptide repeat domain 5), in the regulation of cell signaling pathway and cell viability. TTC5 is a member of the TTC family of proteins and has previously been shown to participate in cellular stress response. Here we demonstrate for the first time that TTC5 significantly activates p53 pathway and inhibits AP-1 transcriptional activity. Further investigation revealed that overexpression of TTC5 up-regulated p53 and p21 expression, and significantly inhibited transcriptional activity, expression and phosphorylation of c-Jun. As for the upstream of signaling pathway of AP-1, our study demonstrated that overexpression of TTC5 significantly down-regulated the expression and phosphorylation of JNK/SAPK. Moreover, overexpression of TTC5 repressed cell proliferation and induced S phase cell cycle arrest. These results indicated that TTC5 may regulate cell viability by p53 and AP-1 signaling pathway.
Mol Biol Rep 2013 Nov
PMID:Human TTC5, a novel tetratricopeptide repeat domain containing gene, activates p53 and inhibits AP-1 pathway. 2409 41