Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Transient Mutator”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,459 records · Page 81Linked to original sources
PubMed1997

The Aspergillus nidulans sepA gene encodes an FH1/2 protein involved in cytokinesis and the maintenance of cellular polarity.

Cytokinesis (septation) in the fungus Aspergillus nidulans occurs through the formation of a transient actin ring at the incipient division site. Temperature-sensitive mutations in the sepA gene prevent septation and cause defects in the maintenance of cellular polarity, without affecting growth and nuclear division. The sepA gene encodes a member of the growing family of FH1/2 proteins, which appear to have roles in morphogenesis and cytokinesis in organisms such as yeast and Drosophila. Results from temperature shift and immunofluorescence microscopy experiments strongly suggest that sepA function requires a preceding mitosis and that sepA acts prior to actin ring formation. Deletion mutants of sepA exhibit temperature-sensitive growth and severe delays in septation at the permissive temperature, indicating that expression of another gene may compensate for the loss of sepA. Conidiophores formed by sepA mutants exhibit abnormal branching of the stalk and vesicle. These results suggest that sepA interacts with the actin cytoskeleton to promote formation of the actin ring during cytokinesis and that sepA is also required for maintenance of cellular polarity during hyphal growth and asexual morphogenesis.

Alleles↗
PubMed2003

Functions of Saccharomyces cerevisiae 14-3-3 proteins in response to DNA damage and to DNA replication stress.

Two members of the 14-3-3 protein family, involved in key biological processes in different eukaryotes, are encoded by the functionally redundant Saccharomyces cerevisiae BMH1 and BMH2 genes. We produced and characterized 12 independent bmh1 mutant alleles, whose presence in the cell as the sole 14-3-3 source causes hypersensitivity to genotoxic agents, indicating that Bmh proteins are required for proper response to DNA damage. In particular, the bmh1-103 and bmh1-266 mutant alleles cause defects in G1/S and G2/M DNA damage checkpoints, whereas only the G2/M checkpoint is altered by the bmh1-169 and bmh1-221 alleles. Impaired checkpoint responses correlate with the inability to maintain phosphorylated forms of Rad53 and/or Chk1, suggesting that Bmh proteins might regulate phosphorylation/dephosphorylation of these checkpoint kinases. Moreover, several bmh1 bmh2Delta mutants are defective in resuming DNA replication after transient deoxynucleotide depletion, and all display synthetic effects when also carrying mutations affecting the polalpha-primase and RPA DNA replication complexes, suggesting a role for Bmh proteins in DNA replication stress response. Finally, the bmh1-169 bmh2Delta and bmh1-170 bmh2Delta mutants show increased rates of spontaneous gross chromosomal rearrangements, indicating that Bmh proteins are required to suppress genome instability.

14-3-3 Proteins↗
PubMed1995

Characterization of alternative amino acid substitutions at arginine 830 of the androgen receptor that cause complete androgen insensitivity in three families.

We have studied two different missense mutations at arginine-830 in exon 7 of the human androgen receptor (hAR) gene that cause complete androgen insensitivity (CAIS) in three families. These substitutions result from point mutations at nucleotide 2489: a G-->T transversion causes Arg830Leu and a G-->A transition causes Arg830Gln. Genital skin fibroblasts of the patients have negligible androgen-binding capacity. The mutations were recreated in an hAR cDNA expression vector that was transiently transfected into COS-1 cells. Both mutant androgen receptors have increased dissociation rate constants and apparent equilibrium rate constants when measured with 5 alpha-dihydrotestosterone or the synthetic, nonmetabolizable androgens, mibolerone or methyltrienolone. The mutant androgen-binding activities share a distinctive thermal misbehavior. At 37 degrees C R830Q and R830L are about 40% and 10% of normal, respectively. At 22 degrees C both mutants gain androgen binding while the normal decreases by 20%; for R830Q the augmented value approaches 60% of the normal. During prolonged 18 h incubation at 37 degrees C, androgen binding of the normal AR is stable while that of both mutants decreases by at least 85%. Both mutants have a very reduced ability to transactivate a cotransfected androgen-responsive reporter gene, but R830Q is better than R830L. We conclude that arginine-830 is important for A-R complex stability, and that its replacement by glutamine or leucine yields distinctive functional aberrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1991

The AP-1 site is required for basal expression but is not necessary for TPA-response of the human stromelysin gene.

We have studied the activity of the AP-1 site, a target for the Fos and Jun family of transcription factors, in the context of the human stromelysin promoter (-1303 to +4). In transiently transfected human HepG2, HeLa and fibroblast cell cultures, point-mutations in any position of the stromelysin AP-1 sequence TGAGTCA (-70 to -64) reduced both the basal level and TPA-induced expression from the stromelysin promoter. TPA-induction fold of the mutant promoters, however, was comparable to that of the wild-type promoter. Similarly, antisense c-Fos mRNA expression reduced basal activity but had no significant effect on the relative TPA-response of the stromelysin promoter. Further, in mouse F9 cells cotransfected with c-Fos and c-Jun expression plasmids, the transfected wild-type stromelysin promoter activity was increased 57-fold whereas no transactivation was detected for an AP-1 mutant stromelysin promoter. In gelshift assays, stromelysin promoter fragments (-101 to -11), containing the mutated AP-1 site, all failed to bind or compete for the in vitro synthesized Fos and Jun proteins. We interpret these data to suggest that the Fos and Jun proteins, or similar activity, and the AP-1 site are required for the basal level expression of the human stromelysin gene. Strikingly, these data also suggest that the stromelysin AP-1 site is not necessary for the TPA-response.

Binding Sites↗
PubMed1994

A proline-rich transcriptional activation domain in murine HOXD-4 (HOX-4.2).

The product of the murine Hoxd-4 (Hox-4.2) gene is a transcription factor that acts upon an autoregulatory element in Hoxd-4 upstream sequences (1). Using this activity as an assay in transient transfections of P19 embryonal carcinoma (EC) cells, we performed a mutational analysis to map functional domains in the HOXD-4 protein. The importance of the homeodomain was shown by a single amino acid change in this region that abolished activity. Deletion analysis revealed that many evolutionarily conserved regions outside of the homeodomain were dispensable for activation in our assay. Fusions to the GAL4 DNA-binding domain mapped a transcriptional activation function to the HOXD-4 proline-rich N-terminus. The proline-rich transcription factor AP2 squelched activation by HOXD-4 and by GAL4/HOXD-4 N-terminus fusion proteins. Together, these results suggest that HOXD-4 harbors a transcriptional activation domain of the proline-rich type.

Amino Acid Sequence↗
PubMed2000

Regulation of tomato leaf curl viral gene expression in host tissues.

The regulation of expression of the two virion-sense (V1 and V2) and four complementary-sense (C1, C2, C3, and C4) open reading frames (ORFs) of Tomato leaf curl virus (TLCV) was studied in both stably and transiently transformed Nicotiana tabacum tissues with fusions with the beta-glucuronidase (GUS) reporter gene. GUS-expressing transgenic lines were obtained with each of the four complementary-sense gene-GUS fusion constructs and with truncated versions of the virion-sense gene-GUS fusion constructs (V1GUSdeltaC and V2GUSdeltaC) lacking complementary-sense sequences encoding the C1, C2, and C3 ORFs. However, little or no GUS expression was observed in kanamycin-resistant plants transformed with full-length, virion-sense gene constructs (V1GUS and V2GUS) constituting the complete viral genome. In contrast, V1GUS and V2GUS were found to direct high-level GUS expression in transient assays with tobacco protoplasts, suggesting that integration of viral constructs containing functional, complementary-sense genes may lead to repression or deletion of the introduced constructs in transgenic tissues. V2GUS expression in the transient protoplast assay was found to be severely curtailed by specific mutation of the C2 ORF, supporting a role for the C2 protein in transactivation of TLCV virion-sense gene expression. TLCV ORF-GUS constructs displayed distinctive tissue expression patterns in transgenic tobacco plants that could be divided into constitutive (C1, C4, and V2GUSdeltaC), predominantly vascular (C2, C3), or reduced expression in cells associated with the vascular bundles (V1GUSdeltaC). The significance of these results is discussed in terms of current models of gene function and regulation in geminiviruses.

Geminiviridae↗
PubMed2001

Characterization of the H1t promoter: role of conserved histone 1 AC and TG elements and dominance of the cap-proximal silencer.

H1t is a testis-specific variant histone 1 gene transcribed in pachytene spermatocytes. As part of a program to understand its transcriptional control, we have investigated the effect of the cap-proximal, GC-rich silencer element in the context of various lengths of upstream sequence. By transient transfection of NIH 3T3 cells, we showed that a targeted mutation in the silencer has a large (>10-fold) effect on reporter gene expression, regardless of the length of upstream sequence present. No other discrete silencing activity was observed in the upstream region extending to nucleotide -1842. Similarly, when the silencer mutation was introduced into the natural gene, H1t expression was readily detected in permanently transfected cells by both RNase protection and Western blot analysis, regardless of the extent of 5' or 3' flanking genomic DNA. In constructs with the mutated silencer, we showed interdependence of the characteristic H1 AC and TG box regulatory elements. Promoter up-regulation occurred only when both were intact, and possibly identical binding factors were demonstrated for each by electrophoretic mobility shift assays. In view of its precisely regulated but limited expression, it is interesting that H1t retains all the promoter elements known to activate standard H1 genes, including the TG/AC unit, SP1 site, and CCAAT element. Their presence emphasizes the apparent dominance of the silencer element in most cells.

3T3 Cells↗
PubMed1992

Mutagenesis of the L protein encoded by Bunyamwera virus and production of monospecific antibodies.

Bacterial fusion proteins containing portions of the Bunyamwera virus L protein were used as immunogens to prepare antisera in rabbits. Of five fusion proteins injected into rabbits, three yielded sera that reacted with the Bunyamwera virus L protein, detected by Western blotting or immunoprecipitation. Two of these antisera were specific for either the amino- or carboxy-terminal regions of the L protein. The specificity of these antisera was confirmed by their pattern of reactivity with full-length and truncated forms of the L protein. Plasmids containing the L gene cDNA under control of a bacteriophage T7 promoter were transfected into CV-1 cells which had previously been infected with a recombinant vaccinia virus, vTF7-3, that expresses T7 RNA polymerase. Antigenically authentic L protein was expressed. Using a nucleocapsid transfection assay developed previously, we showed that the transiently expressed L protein had RNA synthesis activity. Site-specific mutations were made in the L cDNA-containing plasmid to change certain amino acids in the putative polymerase domain of the L protein. The effects of these amino acid substitutions on the RNA synthesis activity of the L protein were monitored using the nucleocapsid transfection assay. These experiments showed that residues strictly conserved between the L proteins of different viruses in the family Bunyaviridae were obligatorily required for activity, whereas non-conserved residues could be substituted without abolishing RNA synthesis capability. Our results provide direct evidence for the functional significance of particular amino acids in the polymerase domain of a negative-strand virus RNA polymerase.

Amino Acid Sequence↗
PubMed1996

Drosophila TFIIA-S is up-regulated and required during Ras-mediated photoreceptor determination.

Photoreceptor induction in the developing Drosophila eye is triggered by the activation of the Ras pathway. Subsequently, the Ras-mediated activation of site-specific transcription factors leads to the expression of putative "effector" genes. The coactivator function of the basal transcription factor TFIIA has been shown previously to enhance the trans-activation potential of site-specific transcription factors in vitro. Here, we show that the expression of the small subunit of TFIIA (dTFIIA-S) is specifically up-regulated in a transient manner during Ras-mediated photoreceptor induction. Furthermore, although null mutations in dTFIIA-S are cell lethal, a hypomorphic dTFIIA-S allele demonstrates an increased requirement for this factor during photoreceptor development. In addition, the cone cell to R7 photoreceptor transformation caused by ectopic activation of the Ras pathway during eye development is suppressed by the removal of one functional copy of the dTFIIA-S locus revealing the sensitivity of this process to reductions in dTFIIA-S activity. These results are the first in vivo evidence for the coactivator function in transcriptional enhancement proposed for TFIIA.

Animals↗
PubMed2004

Transcriptional regulation of the human ABO histo-blood group genes is dependent on the N box upstream of the proximal promoter.

BACKGROUND: Our previous studies of the transcriptional regulation of the human ABO gene indicated that negative regulatory elements are present in the sequence just upstream from the proximal promoter. The role of the -275 to -118 region in regulation of ABO gene transcription is further characterized. STUDY DESIGN AND METHODS: Transient transfection experiments into various cells were performed with luciferase reporter plasmids carrying ABO upstream sequences, and electrophoretic mobility shift assay was carried out with a nuclear extract prepared from the human gastric cancer KATOIII cells. RESULTS: It is shown that the -202 to -118 region is involved in the negative regulation of ABO gene transcription in all cell lines examined. Transient transfection experiments in KATOIII cells with a reporter plasmid carrying mutated N box at -196 to -191 demonstrate that the N box is a negative regulatory element in the -202 to -118 sequence. Electrophoretic mobility shift assays indicate that the N box binds with a nuclear factor from KATOIII cells. CONCLUSION: These results indicate that repression of transcription from the ABO proximal promoter is partially dependent upon the N box. Therefore, reduced binding of the protein with the N box might play a direct role in ABO gene expression.

ABO Blood-Group System↗
PubMed2006

Interferon-gamma down-regulates expression of the 230-kDa bullous pemphigoid antigen gene (BPAG1) in epidermal keratinocytes via novel chimeric sequences of ISRE and GAS.

The 230-kDa bullous pemphigoid antigen (BPAG1) is an integral component of hemidesmosomes. We have previously reported that interferon-gamma (IFNgamma) inhibits the transcription of the BPAG1 gene (1). Here we investigated the target sequences of IFNgamma-signal transduction pathway in the BPAG1 promoter in epidermal keratinocytes. Transient transfections with 5'-deletion constructs of BPAG1 promoter-luciferase reporter gene plasmids in cultured normal human epidermal keratinocytes (NHEK) allowed us to narrow the DNA region containing IFNgamma inhibitory element (IGIE) to between -1 and -89, upstream from the transcription initiation site (+1). Homology search in this region identified a chimeric sequence, consisting of IFN-stimulated responsive element (ISRE) with a partial 7-bp sequence of IFNgamma activation site (GAS), as identified in the guanylate-binding protein (GBP) gene, inserted at its center. Functional analysis of IGIE, inserted in front of the heterologous thymidine kinase promoter, indicated that IGIE acts as a down-regulatory element of the promoter through IFNgamma-dependent signal pathway. Transient transfection studies with BPAG1 promoter-reporter gene constructs containing mutated IGIE (with TT to GG transversions in the region of 5'ISRE, GAS, and 3'ISRE) demonstrated that disruption of the ISRE sequences, but not GAS, markedly suppressed the BPAG1 basal promoter activity and resulted in attenuated IFNgamma response in keratinocytes. Our findings provide novel insight into the mechanism of IFNgamma regulation in keratinocyte differentiation and proliferation.

Base Sequence↗
PubMed2005

Optimizing therapy for myeloid disorders of Down syndrome.

Children with Down syndrome (DS) are at increased risk of leukaemia. Myeloid disorders include transient abnormal myelopoiesis (TAM), myelodysplasia (MDS) and acute myeloid leukaemia (AML). Mutations in the GATA-1 gene, which encodes for a transcription factor central to the normal development of the erythroid and megakaryocytic lineages, are found in cases of TAM, MDS and AML in DS children. DS children with MDS/AML mostly present between the ages of 1 and 4 years, and have a large predominance of megakaryoblastic disease (French-American-British type M7). The MDS and AML are part of a single disease entity (myeloid leukaemia of Down syndrome) that is extremely sensitive to chemotherapy. Resistant disease and relapse are rare, but treatment-related toxicity is high, and deaths in remission have exceeded those due to disease in most series. Accordingly, controlled dosage reduction is the focus of contemporary treatment studies.

Acute Disease↗
PubMed2006

Suppression of engulfment defects in bacillus subtilis by elevated expression of the motility regulon.

During Bacillus subtilis sporulation, the transient engulfment defect of spoIIB strains is enhanced by spoVG null mutations and suppressed by spoVS null mutations. These mutations have opposite effects on expression of the motility regulon, as the spoVG mutation reduces and the spoVS mutation increases sigmaD-directed gene expression, cell separation, and autolysis. Elevating sigmaD activity by eliminating the anti-sigma factor FlgM also suppresses spoIIB spoVG, and both flgM and spoVS mutations cause continued expression of the sigmaD regulon during sporulation. We propose that peptidoglycan hydrolases induced during motility can substitute for sporulation-specific hydrolases during engulfment. We find that sporulating cells are heterogeneous in their expression of the motility regulon, which could result in phenotypic variation between individual sporulating cells.

Bacillus subtilis↗
PubMed1991

Baculovirus gp64 gene expression: analysis of sequences modulating early transcription and transactivation by IE1.

Expression of the baculovirus major envelope glycoprotein gene (gp64) is regulated by transcription from both early and late promoters. To characterize the early promoter and identify sequences involved in the regulation of gp64 early transcription, promoter-reporter gene fusions were generated from the Orygia pseudotsugata nuclear polyhedrosis virus gp64 promoter and were analyzed by transient expression in uninfected insect cells. For these analyses, 5' deletion mutations were constructed in the gp64 upstream regulatory region. Larger promoter constructs were functional in uninfected Lymantria dispar cells, indicating that transcription from the gp64 early promoter required no additional viral gene products. Deletion analysis of the gp64 upstream region revealed several regulatory regions. These included a putative negative regulatory element between -319 and -166 nucleotides (nt) and multiple positive regulatory elements between -166 and -77 nt. Deletion of the TATA box located between -77 and -62 nt resulted in the loss of transcriptional activity. Cotransfections of reporter constructs and a plasmid containing a baculovirus transcriptional transactivator gene (Autographa californica nuclear polyhedrosis virus IE1) resulted in transcriptional transactivation of all constructs containing an intact TATA box. These data demonstrate that sequences upstream of the gp64 TATA box are not essential for IE1 transactivation and that only 34 nt upstream of the early transcription start site were necessary for basal levels of transcription and for transactivation by IE1. Function of the gp64 early promoter was also examined in cell lines from Spodoptera frugiperda and Drosophila melanogaster.

Amino Acid Sequence↗
PubMed1999

Activation of baculovirus very late promoters by interaction with very late factor 1.

Very late factor 1 (VLF-1) of Autographa californica multicapsid nuclear polyhedrosis virus (AcMNPV) activates the transcription of two genes, polyhedrin (polh) and p10, during the final, occlusion-specific phase of infection. Using transient expression assays responsive to VLF-1, we identified linker scan mutations in the polh and p10 promoters which abolished or weakened the ability of the promoters to respond to stimulation by VLF-1. These mutations were located between the transcriptional and translational initiation sites, a region previously shown to be essential for the burst of expression during the very late phase. Addition of partially purified, epitope-tagged VLF-1 to DNA encompassing this "burst sequence" resulted in a shift in the gel electrophoretic mobility of the DNA, indicating that VLF-1 forms a complex with DNA. Addition of an antibody specific for the epitope tag of VLF-1 decreased the mobility of the DNA further, confirming the presence of VLF-1 in the complex. DNase I footprint assays revealed that VLF-1 partially purified from either insect cells or bacterial cells interacted with the burst sequences of both the polh and p10 very-late promoters. Linker scan mutations within the burst sequences severely impaired interaction between VLF-1 and the promoters. We propose that VLF-1 transactivates the polh and p10 promoters by interacting with the burst sequences.

Animals↗
PubMed1998

Epidermal growth factor receptor and the adaptor protein p52Shc are specific substrates of T-cell protein tyrosine phosphatase.

T-cell protein tyrosine phosphatase (TCPTP) exists as two forms generated by alternative splicing: a 48-kDa endoplasmic reticulum (ER)-associated form (TC48) and a 45-kDa nuclear form (TC45). To identify TCPTP substrates, we have generated substrate-trapping mutants, in which the invariant catalytic acid of TCPTP (D182) is mutated to alanine. The TCPTP D182A substrate-trapping mutants were transiently overexpressed in COS cells, and their ability to form complexes with tyrosine-phosphorylated (pTyr) proteins was assessed. No pTyr proteins formed complexes with wild-type TCPTP. In contrast, TC48-D182A formed a complex in the ER with pTyr epidermal growth factor receptor (EGFR). In response to EGF, TC45-D182A exited the nucleus and accumulated in the cytoplasm, where it bound pTyr proteins of approximately 50, 57, 64, and 180 kDa. Complex formation was disrupted by vanadate, highlighting the importance of the PTP active site in the interaction and supporting the characterization of these proteins as substrates. Of these TC45 substrates, the approximately 57- and 180-kDa proteins were identified as p52Shc and EGFR, respectively. We examined the effects of TC45 on EGFR signaling and observed that it did not modulate EGF-induced activation of p42Erk2. However, TC45 inhibited the EGF-induced association of p52Shc with Grb2, which was attributed to the ability of the PTP to recognize specifically p52Shc phosphorylated on Y239. These results indicate that TC45 recognizes not only selected substrates in a cellular context but also specific sites within substrates and thus may regulate discrete signaling events.

3T3 Cells↗
PubMed2000

The epsilon subtype of protein kinase C is required for cardiomyocyte connexin-43 phosphorylation.

Gap junctions (GJs), composed of connexins, are intercellular channels ensuring electric and metabolic coupling between cardiomyocytes. We have shown previously that an endogenous mitogenic and cardioprotective protein, fibroblast growth factor-2 (FGF-2), decreases cardiomyocyte GJ permeability by stimulating phosphorylation of connexin-43 (Cx43). Identifying the kinase(s) phosphorylating cardiac Cx43 may thus provide a way of modulating cardiac intercellular communication. Because FGF-2 activates receptors linked to protein kinase C (PKC) and mitogen-activated protein kinase, we first investigated participation of these enzymatic systems in Cx43 phosphorylation. The inhibitor PD98059 blocked activation of mitogen-activated protein kinase, but it did not prevent the FGF-2 effects on GJs. In contrast, the PKC inhibitor chelerythrine blocked the effects of FGF-2 on Cx43 phosphorylation and permeability. Because the epsilon-isoform of PKC localizes to plasma membrane sites, we examined whether it is directly involved in the FGF-2-induced Cx43 phosphorylation. In nonstimulated myocytes, PKCepsilon displayed a discontinuous pattern of localization at intercellular contact sites and partial colocalization with Cx43. Treatment with FGF-2 or phorbol 12-myristate 13-acetate induced a more continuous pattern of PKCepsilon distribution, whereas the anti-Cx43 staining appeared to overlap extensively with that of PKCepsilon. In immunoprecipitation experiments using specific anti-Cx43 antibodies, PKCepsilon but not PKCalpha coprecipitated with Cx43. FGF-2 increased levels of coprecipitated PKCepsilon, suggesting increased association between PKCepsilon and Cx43 on stimulation. Transient gene transfer and overexpression of cDNAs coding for truncated or mutated dominant-negative forms of PKCepsilon decreased cardiomyocyte Cx43 phosphorylation significantly. We conclude that PKC mediates the FGF-2-induced effects on cardiac GJs and that PKCepsilon likely interacts with and phosphorylates cardiac Cx43 at sites of intercellular contact.

Alkaloids↗
PubMed2006

Polycystin-2 immunolocalization and function in zebrafish.

Polycystin-2 functions as a cation-permeable transient receptor potential ion channel in kidney epithelial cells and when mutated results in human autosomal dominant polycystic kidney disease. For further exploration of the in vivo functions of Polycystin-2, this study examined its expression and function during zebrafish embryogenesis. pkd2 mRNA is ubiquitously expressed, and its presence in the larval kidney could be confirmed by reverse transcription-PCR on isolated pronephroi. Immunostaining with anti-zebrafish Polycystin-2 antibody revealed protein expression in motile kidney epithelial cell cilia and intracellular cell membranes. Intracellular localization was segment specific; in the proximal nephron segment, Polycystin-2 was localized to basolateral cell membranes, whereas in the caudal pronephric segment, Polycystin-2 was concentrated in subapical cytoplasmic vesicles. Polycystin-2 also was expressed in muscle cells and in a variety of sensory cells that are associated with mechanotransduction, including cells of the ear, the lateral line organ, and the olfactory placodes. Disruption of Polycystin-2 mRNA expression resulted in pronephric kidney cysts, body axis curvature, organ laterality defects, and hydrocephalus-defects that could be rescued by expression of a human PKD2 mRNA. In-frame deletions in the first extracellular loop and C-terminal phosphofurin acidic cluster sorting protein-1 (PACS-1) binding sites in the cytoplasmic tail caused Polycystin-2 mislocalization to the apical cell surface. Unlike zebrafish intraflagellar transport protein (IFT) mutants, cyst formation was not associated with cilia defects and instead correlated with reduced kidney fluid output, expansion of caudal duct apical cell membranes, and occlusion of the caudal pronephric nephron segment.

Amino Acid Sequence↗