Transcriptional and subcellular regulation of the TRIP-Br family

Lai, I-Lu; Wang, Shiyun; Yao, Yali; Yang, Wen‐Ming

doi:10.1016/j.gene.2006.10.008

Cited by 28 publications

(32 citation statements)

References 18 publications

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“…TRIP-Br1 and other members of its family contain an N-terminal putative cyclin-A-binding domain, a novel highly conserved SERTA ( Se i-I, R BT1, and TA RA) domain of unclear function, a binding motif for PHD zinc finger- and/or bromodomain-containing proteins, and an acidic C-terminal domain (Lai et al, 2007; Hsu et al, 2001), and these multiple protein-interaction domains in TRIP-Br1 enable it to act as an adaptor/scaffold protein and tethers different signaling components (Hsu et al, 2001; Sim et al, 2006). Moreover, TRIP-Br1 appears to modulate their activity and expression of some of its interacting proteins (Sugimoto et al, 1999; Hong et al, 2011; Lee et al, 2009); however, whether this function of TRIP-Br1 needs a third protein is unclear.…”

Section: Discussionmentioning

confidence: 99%

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The complex of TRIP-Br1 and XIAP ubiquitinates and degrades multiple adenylyl cyclase isoforms

Liu

et al. 2017

eLife

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Adenylyl cyclases (ACs) generate cAMP, a second messenger of utmost importance that regulates a vast array of biological processes in all kingdoms of life. However, almost nothing is known about how AC activity is regulated through protein degradation mediated by ubiquitination or other mechanisms. Here, we show that transcriptional regulator interacting with the PHD-bromodomain 1 (TRIP-Br1, Sertad1), a newly identified protein with poorly characterized functions, acts as an adaptor that bridges the interaction of multiple AC isoforms with X-linked inhibitor of apoptosis protein (XIAP), a RING-domain E3 ubiquitin ligase. XIAP ubiquitinates a highly conserved Lys residue in AC isoforms and thereby accelerates the endocytosis and degradation of multiple AC isoforms in human cell lines and mice. XIAP/TRIP-Br1-mediated degradation of ACs forms part of a negative-feedback loop that controls the homeostasis of cAMP signaling in mice. Our findings reveal a previously unrecognized mechanism for degrading multiple AC isoforms and modulating the homeostasis of cAMP signaling.DOI: http://dx.doi.org/10.7554/eLife.28021.001

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Section: Discussionmentioning

confidence: 99%

“…TRIP-Br1 belongs to a recently discovered protein family that includes TRIP-Br1 (SEI-1, SERTAD1), TRIP-Br2 (SEI-2, SERTAD2), TRIP-Br3 (SEI-3, HEPP, CDCA4), and RBT1 (SERTAD3) in mammals and TARA in Drosophila (Lai et al, 2007; Zang et al, 2009). The functions of TRIP-Br1 and other members of its family have not been fully characterized.…”

Section: Introductionmentioning

confidence: 99%

The complex of TRIP-Br1 and XIAP ubiquitinates and degrades multiple adenylyl cyclase isoforms

Liu

et al. 2017

eLife

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“…To inhibit CRM1-mediated nuclear export, cells were treated with 10 ng/ml LMB for 2 h as described previously (13) prior to immunocytochemical or denaturing SDS-PAGE and WB analyses. Subcellular Fractionation, Denaturing SDS-PAGE, and Western Blotting-Subcellular fractionation of cells was performed using the NE-PER nuclear and cytoplasmic extraction reagents kit (Pierce) in accordance with the manufacturer's instructions.…”

Section: Methodsmentioning

confidence: 99%

“…3I). Notably, Lai et al (13) have recently demonstrated that TRIP-Br2 may be subcellularly localized to the cytoplasm as a result of its association with the CRM1-mediated nuclear export machinery. These data suggest that apart from the 26 S proteasome complex, nuclear export of TRIP-Br2 may also play a role in regulating the turnover of TRIP-Br2.…”

Section: Trip-br2 Is Differentially Expressed During Cell Cyclementioning

confidence: 99%

CRM1-mediated Nuclear Export Is Required for 26 S Proteasome-dependent Degradation of the TRIP-Br2 Proto-oncoprotein

Cheong

Gunaratnam

Hsu

2008

Journal of Biological Chemistry

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Overexpression of the proto-oncogene TRIP-Br2 (SERTAD2) has been shown to induce E2F activity and promote tumorigenesis, whereas ablation of TRIP-Br2 arrests cell proliferation. Timely degradation of many cell cycle regulators is fundamental to the maintenance of proper cell cycle progression. Here we report novel mechanism(s) that govern the tight regulation of TRIP-Br2 levels during cell cycle progression. TRIP-Br2 was observed to be a short-lived protein in which the expression level peaks at the G 1 /S boundary. TRIP-Br2 accumulated in cells treated with 26 S proteasome inhibitors. Co-immunoprecipitation studies revealed that TRIP-Br2 forms ubiquitin conjugates. In silico analysis identified a putative leucine-rich nuclear export signal (NES) motif that overlaps with the PHD-Bromo interaction domain in the acidic C-terminal transactivation domain (TAD) of TRIP-Br2. This NES motif is highly conserved in widely divergent species and in all TRIP-Br family members. TRIP-Br2 was shown to be stabilized in G 2 /M phase cells through nuclear entrapment, either by deletion of the acidic C-terminal TAD, which includes the NES motif, or by leptomycin B-mediated inhibition of the CRM1-dependent nuclear export machinery. Mutation of leucine residue 238 of this NES motif abolished the interaction between CRM1 and TRIP-Br2, as well as the nuclear export of TRIP-Br2 and its subsequent 26 S proteasome-dependent degradation. These data suggest that CRM1-mediated nuclear export may be required for the proper execution of ubiquitin-proteasome-dependent degradation of TRIP-Br2.The TRIP-Br/SERTAD (henceforth referred to as TRIP-Br (transcriptional regulator interacting with the PHD-bromodomain)) family of mammalian transcriptional coregulators has been shown to play important roles in governing cell cycle progression, at least in part, by regulating the expression of E2F-responsive genes that are implicated in or directly linked to the regulation of cell proliferation (1, 2). The mammalian TRIP-Br family comprises four members: TRIP-Br1/p34SEI-1 /SER-TAD1/SEI-1 (henceforth referred to as TRIP-Br1); TRIP-Br2/ SERTAD2/SEI-2 (henceforth referred to as TRIP-Br2); TRIPBr3/HEPP/CDCA4/SEI-3 (henceforth referred to as TRIPBr3); and RBT1 3 (replication protein A-binding transactivator 1)/SERTAD3 (henceforth referred to as RBT1) (3). In addition, the TRIP-Br homolog in Drosophila, Taranis (TARA), was identified in a screen for functional partners of the homeotic loci and was shown to represent a novel member of the trithorax group of regulatory proteins (4). TRIP-Br proteins are recruited to the retinoblastoma (Rb) protein-dissociated E2F-1⅐DP-1 complexes on E2F-responsive promoters through physical association with DP-1. PHD zinc finger-and/or bromodomain-containing proteins such as p300/CBP, PCAF, and KRIP-1, present in differing amounts and possessing different binding affinities, have been proposed to compete for binding to TRIP-Br proteins and confer positive or negative regulatory signals to E2F-1⅐DP-1 transcription complexes assembl...

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“…With its initial name as murine Hepp (hematopoietic progenitor protein), CDCA4 was first detected in hematopoietic progenitor cells and was considered to be involved in blood cell development in embryos [Abdullah et al, 2001]. CDCA4 was also categorized as SEI3 of SEI protein family as well as TRIP-Br3 of TRIP-Br family, both based on their homologous sequence motifs including SERTA and a PHD-bromo-binding site which interacts with a series of bromodomain containing transcriptional cofactors [Watanabe-Fukunaga et al, 2005;Lai et al, 2007]. In addition, CDCA4 was found to be able to enhance the trans-activation function of p53 [Watanabe-Fukunaga et al, 2005].…”

Section: Introductionmentioning

confidence: 99%

The spindle function of CDCA4

Wang

Zhu

Yang

et al. 2008

Cell Motil. Cytoskeleton

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In an attempt to discover novel proteins functioning in both interphase nucleus and mitotic spindle as NuMA does, we carried out cDNA library screening with pooled autoimmune antibodies. Among positive clones we found a recently identified transcription regulatory protein (CDCA4) with the distinctive nuclear-mitotic apparatus distribution. CDCA4 localizes at metaphase spindle poles and the midzone in later stages. Additionally, an intensive CDCA4 accumulation parallel to spindle was observed in half of metaphase cells but not in later stages, implying a transient form of CDCA4 binding to midzone from anaphase. Mitotic arrest dissolved CDCA4 from centrosomes but during the spindle recovery, CDCA4 invariably colocalized with the microtubule nucleation foci as a component of microtubule organization center. RNA interference of CDCA4 resulted in significant increase of multinuclei and multipolar spindles, suggesting impaired function in chromosome segregation or cytokinesis. However, the spindle checkpoint and the centrosome cycle appeared not to be affected by such interference. Furthermore, CDCA4 depletion resulted in accelerated cell proliferation, perhaps due to the disruption of CDCA4 nuclear function as a transcription suppressor. Interphase CDCA4 is localized in nucleoli by immunofluorescence, although GFP-CDCA4 expressed in the nucleoplasm. An N-terminal KRKC domain appears to be the nuclear localization signal as identified by sequence alignment and the expression of truncated mutants. Taken together, our results suggested that as a novel nuclearmitotic apparatus protein, CDCA4 is involved in spindle organization from prometaphase. When anaphase begins, CDCA4 may play a different role as a midzone factor involved in chromosome segregation or cytokinesis. Cell Motil. Cytoskeleton 65: 581-593, 2008. '

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Transcriptional and subcellular regulation of the TRIP-Br family

Cited by 28 publications

References 18 publications

The complex of TRIP-Br1 and XIAP ubiquitinates and degrades multiple adenylyl cyclase isoforms

The complex of TRIP-Br1 and XIAP ubiquitinates and degrades multiple adenylyl cyclase isoforms

CRM1-mediated Nuclear Export Is Required for 26 S Proteasome-dependent Degradation of the TRIP-Br2 Proto-oncoprotein

The spindle function of CDCA4

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