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Christopher D Richards, Coral G Warr, Richard Burke
Dietary zinc is the principal source of zinc in eukaryotes, with its uptake and distribution controlled by a complex network of numerous membrane-spanning transport proteins. Dietary absorption is achieved by members of the SLC39A (ZIP) gene family, which encode proteins that are generally responsible for the movement of zinc into the cytosol. ZIP4 is thought to be the primary mammalian zinc uptake gene in the small intestine, with mutations in this gene causing the zinc deficiency disease Acrodermatitis enteropathica...
December 2015: International Journal of Biochemistry & Cell Biology
Boyan Zhang, Tingting Zhang, Guopeng Wang, Gang Wang, Wangfei Chi, Qing Jiang, Chuanmao Zhang
The primary cilium, which disassembles before mitotic entry and reassembles after mitosis, organizes many signal transduction pathways that are crucial for cell life and individual development. However, how ciliogenesis is regulated during the cell cycle remains largely unknown. Here we show that GSK3β, Dzip1, and Rab8 co-regulate ciliogenesis by promoting the assembly of the ciliary membrane after mitosis. Immunofluorescence and super-resolution microscopy showed that Dzip1 was localized to the periciliary diffusion barrier and enriched at the mother centriole...
April 2015: PLoS Biology
Ye J Ha, Chan W Kim, Seon A Roh, Dong H Cho, Jong L Park, Seon Y Kim, Jong H Kim, Eun K Choi, Yong S Kim, Jin C Kim
PURPOSE: Prediction of individual responsiveness to preoperative chemoradiation therapy (CRT) is urgently needed in patients with poorly responsive locally advanced rectal cancer (LARC). METHODS AND MATERIALS: Candidate methylation genes associated with radiosensitivity were identified using a 3-step process. In the first step, genome-wide screening of methylation genes was performed in correlation with histopathologic tumor regression grade in 45 patients with LARC...
March 1, 2015: International Journal of Radiation Oncology, Biology, Physics
Kesang Dechen, Christopher D Richards, Jessica C Lye, Joab E C Hwang, Richard Burke
Movement of zinc ions across cellular membranes is achieved mainly by two families of zinc transport genes encoding multi-transmembrane domain proteins. Members of the Zip family generally transport zinc into the cytosol, either from outside the cell or from the lumen of subcellular organelles such as the endoplasmic reticulum, Golgi, endosomes or storage vacuoles. ZnT proteins move zinc in the opposite direction, resulting in efflux from the cell or uptake into organelles. Zinc homeostasis at both the cellular and systemic level is achieved by the coordinated action of numerous Zip and ZnT proteins, twenty-four in mammals and seventeen in the vinegar fly Drosophila melanogaster...
March 2015: International Journal of Biochemistry & Cell Biology
Corey R Arnold, Ryan E Lamont, John T Walker, Peter J Spice, Chi-Kin Chan, Chi-Yip Ho, Sarah J Childs
BACKGROUND: The zebrafish genetic mutant iguana (igu) has defects in the ciliary basal body protein Dzip1, causing improper cilia formation. Dzip1 also interacts with the downstream transcriptional activators of Hedgehog (Hh), the Gli proteins, and Hh signaling is disrupted in igu mutants. Hh governs a wide range of developmental processes, including stabilizing developing blood vessels to prevent hemorrhage. Using igu mutant embryos and embryos treated with the Hh pathway antagonist cyclopamine, we conducted a microarray to determine genes involved in Hh signaling mediating vascular stability...
February 2015: Developmental Dynamics: An Official Publication of the American Association of Anatomists
Patrícia Shigunov, Jose Sotelo-Silveira, Marco Augusto Stimamiglio, Crisciele Kuligovski, Florencia Irigoín, Jose L Badano, David Munroe, Alejandro Correa, Bruno Dallagiovanna
BACKGROUND: DZIP1 (DAZ-interacting protein 1) has been described as a component of the Hh signaling pathway with a putative regulatory role in ciliogenesis. DZIP1 interacts with DAZ RNA binding proteins in embryonic stem cells and human germ cells suggesting a role in mRNA regulation. RESULTS: We investigated DZIP1 function in HeLa cells and its involvement in ribonucleoprotein complexes. DZIP1 was predominantly located in granules in the cytoplasm. Under oxidative stress conditions, DZIP1 re-localized to stress granules...
2014: BMC Molecular Biology
Tyler Schwend, Zhigang Jin, Kai Jiang, Brian J Mitchell, Jianhang Jia, Jing Yang
The Hedgehog (Hh) pathway is essential for embryonic development and adult tissue homeostasis. The Gli/Cubitus interruptus (Ci) family of transcription factors acts at the downstream end of the pathway to mediate Hh signaling. Both Hh-dependent and -independent Gli regulatory mechanisms are important for the output of Hh signaling. Daz interacting protein 1 (Dzip1) has bipartite positive and negative functions in the Hh pathway. The positive Hh regulatory function appears to be attributed to a requirement for Dzip1 during ciliogenesis...
November 8, 2013: Journal of Biological Chemistry
Qiuhong Qin, Xiaoxi Wang, Bing Zhou
BACKGROUND: Zinc is key to the function of many proteins, but the process of dietary zinc absorption is not well clarified. Current knowledge about dietary zinc absorption is fragmented, and mostly derives from incomplete mammalian studies. To gain a comprehensive picture of this process, we systematically characterized all zinc transporters (that is, the Zip and ZnT family members) for their possible roles in dietary zinc absorption in a genetically amenable model organism, Drosophila melanogaster...
2013: BMC Biology
Chengbing Wang, Wee-Chuang Low, Aimin Liu, Baolin Wang
The primary cilium is required for Hedgehog signaling. So far, all known ciliogenic proteins regulate Hedgehog signaling through their role in ciliogenesis. Here we show that the mouse DZIP1 regulates Hedgehog signaling through two mechanisms. First, DZIP1 interacts with GLI3, a transcriptional regulator for Hedgehog signaling, and prevents GLI3 from entering the nucleus. Second, DZIP1 is required for ciliogenesis. We show that DZIP1 colocalizes and interacts with CEP164, a protein localizing at appendages of the mother centrioles, and IFT88, a component of the intraflagellar transport (IFT) machinery...
October 11, 2013: Journal of Biological Chemistry
Xin-Xian Zhang, Di Huang, Nan-Nan Liu, Jie Li, Ri-Yang Lin, Xin-Zhi Zhang, Feng Wu, Li-Qun He
OBJECTIVE: To explore the abnormal expressions of testicular reproduction-related genes induced by glycosides of Tripterygium wilfordii (GTW) and the intervention with kidney-tonifying Chinese herbs. METHODS: Adult Balb/C male mice were fed on GTW at 30 mg per kg per d for 3 weeks to establish a model of reproductive dysfunction. The model mice were divided into different groups to receive intragastrical administration of saline (0.25 ml/d), GTW (30 mg per kg per d), Cistanche (10 g per kg per d), Rehmannia (10 g per kg per d), and Rehmannia + Cistanche (20 g per kg per d), respectively, once a day for 3 weeks...
May 2012: Zhonghua Nan Ke Xue, National Journal of Andrology
Minglin Lang, Lei Wang, Qiangwang Fan, Guiran Xiao, Xiaoxi Wang, Yi Zhong, Bing Zhou
The aggregation or oligomerization of amyloid-β (Aβ) peptide is thought to be the primary causative event in the pathogenesis of Alzheimer's disease (AD). Considerable in vitro evidence indicates that the aggregation/oligomerization of Aβ is promoted in the presence of Zn; however, the functional role of Zn in AD pathogenesis is still not well clarified in vivo. Zn is imported into the brain mainly through the solute-linked carrier (Slc) 39 family transporters. Using a genetically tractable Drosophila model, we found that the expression of dZip1, the orthologue of human Slc39 family transporter hZip1 in Drosophila, was altered in the brains of Aβ42-expressing flies, and Zn homeostasis could be modulated by forcible dZip1 expression changes...
2012: PLoS Genetics
Mizuho Kikuyama, Hideyuki Takeshima, Takayuki Kinoshita, Eriko Okochi-Takada, Mika Wakabayashi, Sadako Akashi-Tanaka, Toshihisa Ogawa, Yasuyuki Seto, Toshikazu Ushijima
Identification of tumor-suppressor genes (TSGs) silenced by aberrant methylation of promoter CpG islands (CGIs) is important, but hampered by a large number of genes methylated as passengers of carcinogenesis. To overcome this issue, we here took advantage of the fact that the vast majority of genes methylated in cancers lack, in normal cells, RNA polymerase II (Pol II) and have trimethylation of histone H3 lysine 27 (H3K27me3) in their promoter CGIs. First, we demonstrated that three of six known TSGs in breast cancer and two of three in colon cancer had Pol II and lacked H3K27me3 in normal cells, being outliers to the general rule...
September 28, 2012: Cancer Letters
André X C N Valente, Joo H Shin, Abhijit Sarkar, Yuan Gao
An association between a rare, coding, non-synonymous SNP variant in the gene DZIP1 and Parkinson's disease was found, based on an analysis of the existing NGRC genome-wide association study dataset. The statistical analysis utilized the hypothesis-rich, targeted search unbiased assessment approach, rather than the hypothesis-free, genome-wide agnostic search paradigm. The association of DZIP1 with Parkinson's disease is discussed in the context of a Parkinson's disease stem-cell ageing theory.
2012: Scientific Reports
Zhigang Jin, Wenyan Mei, Stefan Strack, Jianhang Jia, Jing Yang
The Hedgehog (Hh) pathway is evolutionarily conserved and plays critical roles during embryonic development and adult tissue homeostasis. Defective Hh signaling has been linked to a wide range of birth defects and cancers. Hh family proteins regulate the expression of their downstream target genes through the control of proteolytic processing and the transcriptional activation function of Gli transcription factors. Although Hh-dependent regulation of Gli has been studied extensively, other Gli regulatory mechanisms remain relatively unappreciated...
October 21, 2011: Journal of Biological Chemistry
Hyejeong Rosemary Kim, Joanna Richardson, Freek van Eeden, Philip W Ingham
BACKGROUND: In mammalian cells, the integrity of the primary cilium is critical for proper regulation of the Hedgehog (Hh) signal transduction pathway. Whether or not this dependence on the primary cilium is a universal feature of vertebrate Hedgehog signalling has remained contentious due, in part, to the apparent divergence of the intracellular transduction pathway between mammals and teleost fish. RESULTS: Here, using a functional Gli2-GFP fusion protein, we show that, as in mammals, the Gli2 transcription factor localizes to the primary cilia of cells in the zebrafish embryo and that this localization is modulated by the activity of the Hh pathway...
2010: BMC Biology
Ryan E Lamont, Wendy Vu, Alyson D Carter, Fabrizio C Serluca, Calum A MacRae, Sarah J Childs
The molecular pathways by which newly formed, immature endothelial cell tubes remodel to form a mature network of vessels supported by perivascular mural cells are not well understood. The zebrafish iguana (igu) genetic mutant has a mutation in the daz-interacting protein 1 (dzip1), a member of the hedgehog signaling pathway. Loss of dzip1 results in decreased size of the cranial dorsal aortae, ultrastructural defects in perivascular mural cell recruitment and subsequent hemorrhage. Although hedgehog signaling is disrupted in igu mutants, we find no defects in vessel patterning or artery-vein specification...
April 2010: Mechanisms of Development
Shang Yew Tay, Xianwen Yu, Kangli Noel Wong, Pallavi Panse, Chee Peng Ng, Sudipto Roy
Cilia play important roles in many developmental and physiological processes. However, the genetic and cell biological control of ciliogenesis remains poorly understood. Here, we show that the zebrafish iguana gene is required for differentiation of primary cilia. iguana encodes a zinc finger and coiled-coil containing protein, previously implicated in Hedgehog signaling. We now argue that aberrant Hedgehog activity in iguana -deficient zebrafish arises from their profound lack of primary cilia. By contrast, the requirement of iguana for motile cilia formation is less obligatory...
February 2010: Developmental Dynamics: An Official Publication of the American Association of Anatomists
Andrew M Glazer, Alex W Wilkinson, Chelsea B Backer, Sylvain W Lapan, Jennifer H Gutzman, Iain M Cheeseman, Peter W Reddien
Hedgehog signaling is critical for metazoan development and requires cilia for pathway activity. The gene iguana was discovered in zebrafish as required for Hedgehog signaling, and encodes a novel Zn finger protein. Planarians are flatworms with robust regenerative capacities and utilize epidermal cilia for locomotion. RNA interference of Smed-iguana in the planarian Schmidtea mediterranea caused cilia loss and failure to regenerate new cilia, but did not cause defects similar to those observed in hedgehog(RNAi) animals...
January 1, 2010: Developmental Biology
Katherine L Hammond, Tanya T Whitfield
In zebrafish, Hedgehog (Hh) signalling is required to specify posterior otic identity. This presents a conundrum, as the nearest source of Hh to the developing inner ear is the ventral midline, in the notochord and floorplate. How can a source of Hh that is ostensibly constant with respect to the anteroposterior axis of the otic vesicle specify posterior otic identity? One possibility is that localised inhibition of Hh signalling is involved. Here we show that genes coding for three inhibitors of Hh signalling, su(fu), dzip1 and hip, are expressed in and around the developing otic vesicle...
September 2009: Gene Expression Patterns: GEP
Yuriko Katoh, Masaru Katoh
Hedgehog, BMP/TGFbeta, FGF, WNT and Notch signaling pathways constitute the stem cell signaling network, which plays a key role in a variety of processes, such as embryogenesis, maintenance of adult tissue homeostasis, tissue repair during chronic persistent inflammation, and carcinogenesis. Sonic hedgehog (SHH), Indian hedgehog (IHH) and Desert hedgehog (DHH) bind to PTCH1/PTCH or PTCH2 receptor to release Smoothened (SMO) signal transducer from Patched-dependent suppression. SMO then activates STK36 serine/threonine kinase to stabilize GLI family members and to phosphorylate SUFU for nuclear accumulation of GLI...
December 2006: International Journal of Molecular Medicine
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