Calsenilin interacts with transcriptional co‐repressor C‐terminal binding protein(s)

Zaidi, Nikhat F.; Kuplast, Kristy G.; Washicosky, Kevin J.; Kajiwara, Yuji; Buxbaum, Joseph D.; Wasco, Wilma

doi:10.1111/j.1471-4159.2006.03972.x

Cited by 22 publications

(22 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Especially KChIP3, but also KChIP1, KChIP2 and KChIP4, may fulfill the function of a transcriptional repressor, either directly, by binding to downstream regulatory element (DRE) sites of genes [19,55–61], or indirectly, by binding to other transcription factors [62–64]. Here the focus is put on direct KChIP-mediated control of gene transcription (Figure 1C), which appears to be commonly linked to excitability.…”

Section: Kchips Control Gene Transcriptionmentioning

confidence: 99%

Kv channel-interacting proteins as neuronal and non-neuronal calcium sensors

Bähring

2018

Channels

View full text Add to dashboard Cite

Kv channel-interacting proteins (KChIPs) belong to the neuronal calcium sensor (NCS) family of Ca2+-binding EF-hand proteins. KChIPs constitute a group of specific auxiliary β-subunits for Kv4 channels, the molecular substrate of transient potassium currents in both neuronal and non-neuronal tissues. Moreover, KChIPs can interact with presenilins to control ER calcium signaling and apoptosis, and with DNA to control gene transcription. Ca2+ binding via their EF-hands, with the consequence of conformational changes, is well documented for KChIPs. Moreover, the Ca2+ dependence of the presenilin/KChIP complex may be related to Alzheimer’s disease and the Ca2+ dependence of the DNA/KChIP complex to pain sensing. However, only in few cases could the Ca2+ binding to KChIPs be directly linked to the control of excitability in nerve and muscle cells known to express Kv4/KChIP channel complexes. This review summarizes current knowledge about the Ca2+ binding properties of KChIPs and the Ca2+ dependencies of macromolecular complexes containing KChIPs, including those with presenilins, DNA and especially Kv4 channels. The respective physiological or pathophysiolgical roles of Ca2+ binding to KChIPs are discussed.

show abstract

Section: Kchips Control Gene Transcriptionmentioning

confidence: 99%

Kv channel-interacting proteins as neuronal and non-neuronal calcium sensors

Bähring

2018

Channels

View full text Add to dashboard Cite

show abstract

“…It was further discovered that binding of calcium to these EF regions resulted in a change in configuration that impairs interaction of the DREAM molecule with DNA (Osawa et al, 2001). Recent studies utilizing yeast two-hybrid screening reveals that DREAM also has the capacity to interact with a number of proteins in different cellular compartments (Savignac et al, 2005;Zaidi et al, 2006). Our demonstration that DREAM is expressed in GT1-7 cells and that it is a part of the OCT1BS-a binding complex supports its involvement in the process of NSE-related GnRH promoter activity.…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies revealed that in addition to direct binding to DNA through downstream regulatory elements (DRE), DREAM can also interact and modulate the action of transcriptional factors through protein-protein interaction (Ledo et al, 2002;Rivas et al, 2004;Zaidi et al, 2006). In the NSE region of the GnRH promoter, there are no sequences that offer a high degree of homology to consensus DRE sequence.…”

Section: Emsa Analysis Of Dream Binding To the Oct1bs-a Sitementioning

confidence: 99%

Calcium influx and DREAM protein are required for GnRH gene expression pulse activity

Leclerc

Boockfor

2007

Molecular and Cellular Endocrinology

View full text Add to dashboard Cite

Recent evidence using GT1-7 cells indicates that GnRH pulsatility depends on exocytotic-release and gene transcription events. To determine whether calcium or DREAM may play a role in linking these processes, we used an L-type Ca 2+ -blocker (nimodipine) and found that not only GnRH gene expression (GnRH-GE) pulse activity was abolished but also that binding of proteins to OCT1BS-a (essential site for GnRH-GE pulses) was reduced. We further found that only EF-hand forms of DREAM were expressed in GT1-7 and that DREAM was part of the complex binding to OCT1BS-a. Finally, microinjection of DREAM antibody into cells abolished GnRH-GE pulses demonstrating its importance in pulsatility. These results reveal that calcium and DREAM may bridge cytoplasmic and nuclear events enabling temporal coordination of intermittent activity. Expression of DREAM in various cell types coupled with the universal role of calcium raise the possibility that these factors may play similar role in other secretory cells.

show abstract

“…Interestingly, although the binding is insensitive to Ca 2+ , regulation of the gating needs the integrity of the EF-hands in the DREAM protein [3]. In another yeast two-hybrid assay, using the N-terminal of DREAM as bait the interactions with the transcriptional corepressor C-terminal binding protein 2 (CtBP2) and its homolog CtBP1 were identified [16]. Interestingly, histone deacetylase (HDAC) protein and activity was found to be associated with the DREAM-CtBP immunocomplex, sug- gesting a mechanism by which DREAM-CtBP may act to repress transcription.…”

Section: Defining the Dream Interactomementioning

confidence: 99%

“…For instance, DRE sites contribute to basal and induced expression of a number of immediate early transcription factors including c-fos, c-jun and ICER [2,4]. In addition to its regulation by calcium, binding of DREAM to DNA is hampered by its interaction with phosphoCREM [14], while interaction with other transcription factors like CREB, TTF-1 or CtBP2 allows DREAM to regulate transcription of genes that do not contain DRE sites ( Figure 2) [7,15,16]. Outside the nucleus, DREAM regulates many cellular functions through selective interactions with an increasing number of proteins that constitute the DREAM interactome and underscore DREAM multifunctional properties.…”

Section: Dream a Multifunctional Proteinmentioning

confidence: 99%

Building the DREAM interactome

Rivas

Villar²,

González³

et al. 2011

Sci. China Life Sci.

View full text Add to dashboard Cite

DREAM/calsenilin/KChIP3 is a calcium binding protein of the neuronal calcium sensor superfamily. DREAM interacts with DRE (downstream regulatory element) sites in the DNA to regulate transcription and with many proteins to exert specialized functions in different subcellular compartments. Work from different laboratories has identified a growing list of interacting proteins that constitutes the DREAM interactome. The knowledge of these interactions has greatly contributed to the understanding of the various physiological functions of DREAM. 1 DREAM, a multifunctional protein DREAM (Antagonist Modulator of DRE sites) was cloned in a functional screening of a cDNA library from human striatum as a transcriptional repressor able to form tetramers and bind to the DRE site in the proximal promoter of the human prodynorphin gene [1,2]. DREAM is expressed in brain, thyroid gland, immune system, heart and gonads and is one of four highly conserved members of the KChIP (potassium channel interacting protein) subfamily of neuronal calcium sensors [3,4]. DREAM, also known as calsenilin [5] or KChIP3 [3], is a calcium binding protein that contains three functional EF-hand motifs (Figure 1) and interacts with DRE (downstream regulatory element) sites in the DNA and with many proteins to exert specialized functions in different subcellular compartments [6]. Binding of calcium induces a structural change in DREAM that precludes binding to DNA and modifies the interaction with some proteins but not with others. For instance, Ca 2+ -bound DREAM does not interact with CREB [7] or with the PSD-95 protein [8], while the interaction of DREAM with presenilins [5], with potassium channels of the Kv4 class [3] or with the TSH receptor [9], is not affected by calcium.A key property of DREAM is the ability to form homomers or heterotetramers with other KChIP proteins, which results in different affinities for DNA binding to DRE sites proximal to the transcription start site, leading to transcriptional repression of target genes [2,4,10,11]. The DRE sequence was defined as the element responsible for basal and induced expression of the prodynorphin gene, encoding a protein involved in nociception as well as in learning and memory [12,13]. More recent studies, however, have shown that many other genes also contain DRE sites and are regulated by DREAM. For instance, DRE sites contribute to basal and induced expression of a number of immediate early transcription factors including c-fos, c-jun and ICER [2,4]. In addition to its regulation by calcium, binding of DREAM to DNA is hampered by its interaction with phosphoCREM [14], while interaction with other transcription

show abstract

Calsenilin interacts with transcriptional co‐repressor C‐terminal binding protein(s)

Cited by 22 publications

References 47 publications

Kv channel-interacting proteins as neuronal and non-neuronal calcium sensors

Kv channel-interacting proteins as neuronal and non-neuronal calcium sensors

Calcium influx and DREAM protein are required for GnRH gene expression pulse activity

Building the DREAM interactome

Contact Info

Product

Resources

About