• Title/Summary/Keyword: regulating a family

Search Result 141, Processing Time 0.023 seconds

A 100 kDa Protein Binding to bHLH Family Consensus Recognition Sequence of RAT p53 Promoter

  • Lee, Min-Hyung;Park, Sun-Hee;Song, Hai-Sun;Lee, Kyung-Hee;Park, Jong-Sang
    • BMB Reports
    • /
    • v.30 no.3
    • /
    • pp.205-210
    • /
    • 1997
  • p53 tumor suppressor plays an important role in the regulation of cellular proliferation. To identify proteins regulating the expression of p53 in rat liver, we analyzed p53 promoter by electrophoretic mobility shift assay (EMSA) and DNase I footprinting assay. We found that a protein binds the sequence CACGTG, bHLH consensus sequence in rat p53 promoter. Southwestern blotting analysis with oligonucleotides containing this sequence shows that the molecular weight of the protein is 100 kDa. This size is not compatible with the bHLH family such as USF or c-Myc/Max which is known to regulate the expression of the human and mouse p53 gene. Therefore this 100 kDa protein may be a new protein regulating basal transcription of rat p53. We purified this 100 kDa protein through sequence-specific DNA affinity chromatogaphy.

  • PDF

ALEX1 Regulates Proliferation and Apoptosis in Breast Cancer Cells

  • Gao, Yue;Wu, Jia-Yan;Zeng, Fan;Liu, Ge-Li;Zhang, Han-Tao;Yun, Hong;Song, Fang-Zhou
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.16 no.8
    • /
    • pp.3293-3299
    • /
    • 2015
  • Background: Arm protein lost in epithelial cancers, on chromosome X (ALEX) is a novel subgroup within the armadillo (ARM) family, which has one or two ARM repeat domains as opposed to more than six-thirteen repeats in the classical Armadillo family members. Materials and Methods: In the study, we explore the biological functions of ALEX1 in breast cancer cells. Overexpression of ALEX1 and silencing of ALEX1 were performed with SK-BR3 and MCF-7 cell lines. Cell proliferation and colony formation assays, along with flow cytometry, were carried out to evaluate the roles of ALEX1. Results: ALEX1 overexpression in SK-BR3 breast cancer cells inhibited proliferation and induced apoptosis. Furthermore, depletion of ALEX1 in MCF-7 breast cancer cells increased proliferation and inhibited apoptosis. Additional analyses demonstrated that the overexpression of ALEX1 activated the intrinsic apoptosis cascades through up-regulating the expression of Bax, cytosol cytochrome c, active caspase-9 and active caspase-3 and down-regulating the levels of Bcl-2 and mitochondria cytochrome c. Simultaneouly, silencing of ALEX1 inhibited intrinsic apoptosis cascades through down-regulating the expression of Bax, cytosol cytochrome c, active caspase-9, and active caspase-3 and up-regulating the level of Bcl-2 and mitochondria cytochrome c. Conclusions: Our data suggest that ALEX1 as a crucial tumor suppressor gene has been involved in cell proliferation and apoptosis in breast cancer, which may serve as a novel candidate therapeutic target.

The Role of Tripartite Motif Family Proteins in TGF-β Signaling Pathway and Cancer

  • Lee, Ho-Jae
    • Journal of Cancer Prevention
    • /
    • v.23 no.4
    • /
    • pp.162-169
    • /
    • 2018
  • $TGF-{\beta}$ signaling plays a tumor suppressive role in normal and premalignant cells but promotes tumor progression during the late stages of tumor development. The $TGF-{\beta}$ signaling pathway is tightly regulated at various levels, including transcriptional and post-translational mechanisms. Ubiquitination of signaling components, such as receptors and Smad proteins is one of the key regulatory mechanisms of $TGF-{\beta}$ signaling. Tripartite motif (TRIM) family of proteins is a highly conserved group of E3 ubiquitin ligase proteins that have been implicated in a variety of cellular functions, including cell growth, differentiation, immune response, and carcinogenesis. Recent emerging studies have shown that some TRIM family proteins function as important regulators in tumor initiation and progression. This review summarizes current knowledge of TRIM family proteins regulating the $TGF-{\beta}$ signaling pathway with relevance to cancer.

Simazine-induced Alteration of the Expression Levels of Apoptosis- and Steroidogenesis-regulating Genes in Testicular Cells (Simazine이 정소세포에서 Apoptosis와 Steroidogenesis 조절 유전자들의 발현에 미치는 영향)

  • Park, Ho-Oak;Ko, Jeong-Jae;Bae, Jee-Hyeon
    • Development and Reproduction
    • /
    • v.15 no.2
    • /
    • pp.159-166
    • /
    • 2011
  • Simazine (6-chloro-N,N'-diethyl-1,3,5-triazine-2,4-diamine) is a triazine herbicide that has been applied worldwide including Korea for agricultural purposes. Simazine is the second most commonly detected pesticide in surfaceand ground-water in the United States, Europe and Australia. It has been shown that simazine is a potent endocrine disruptor in wildlife and laboratory animals. Although many endocrine disruptors can induce apoptosis in various types of cells, the effects of simazine on apoptosis and on the expression of Bcl-2 family genes are not known. Also it is unknown the effect of simazine on the expression of steroidogenesis-regulating genes in testicular cells. In this study, we investigated the effect of simazine on the expression levels of apoptosis- and steroidogenesis-regulating genes in testicular cells. We found that a low concentration of simazine can alter the mRNA expression levels of steroidogenesis-related genes and Bcl-2 family genes in mouse Sertoli cells and rat Leydig cells. Thus, our results suggest that simazine can disturb normal testicular development and reproductive function by altering the expression of genes that are critical for the regulation of apoptosis and steroidogenesis.

Development of Anti-Melanogenic Agent for Skin Whitening

  • Ahn, Soo-Mi
    • Proceedings of the Korean Society of Applied Pharmacology
    • /
    • 2007.11a
    • /
    • pp.129-139
    • /
    • 2007
  • Many modalities of treatment for acquired skin hyperpigmentation are available including chemical agents or physical therapies, but none are completely satisfactory. The ideal depigmenting compound should have a potent. rapid and selective bleaching effect on hyperactivated melanocytes, carry no short- or long-term side-effects and lead to a permanent removal of undesired pigment. acting at one or more steps of the pigmentation process. Depigmentation can be achieved by regulating (i) the transcription and activity of tyrosinase, tyrosinase related protein-1 (TRP-1), tyrosinase related protein-2 (TRP-2), and/or peroxidase; (ii) the uptake and distribution of melanosomes in recipient keratinocytes and (iii) melanin and melanosome degradation and turnover of pigmented keratinocytes. One of the interesting point for development of skin whitening agent is Mitf(Microphthalmia-associated transcription factor). Mitf belongs to the basic helix-loop-helix-zip family of trabscription factors and it is crucial as it regulates both melanocyte proliferation as well as melanogenesis and is the major regulator of tyrosinase and the related enzymes (TRPs), as well as many melanosome structural proteins such as pMel17. Recently, we developed MITF-down-regulating agents from natural and synthetic sources, which have anti-melanogenic effect on in vitro and in vivo. We suggested that potent MITF-down regulating agents might be used for skin whitening cosmeceuticals.

  • PDF

The Planning Concepts and Design Principles of Dok-Rak-Dang Block (독락당(獨樂堂) 일곽(一郭)의 계획개념과 설계원리)

  • Jang, Sun-Joo
    • Journal of the Korean housing association
    • /
    • v.24 no.6
    • /
    • pp.93-101
    • /
    • 2013
  • This research purposes to understand architectural aim which the owners of buildings in the Doa-Rak-Dang block pursue through the history of family and construction. Moreover its other purpose is to find the design concepts which were selected to achieve the aim and the design elements which were applied to realize the design concepts. To accomplish the objects, it got rid of a stationary viewpoint but it approached with a dynamic viewpoint which can read the changes in the steps during various periods. Through the 100-year history of construction, the architectural aim of the Doa-Rak-Dang block is to establish the tradition of the Ok-San-Pa family to get over the social limitations of the family of a child by a concubine which began from Lee, Eun-Juk's mistress. The design concepts which were used by the owners of the Dok-Rak-Dang block to achieve the purpose are the extension of public territory and the enrichment of territoriality which have social-political, economical and symbolic means. The geometric applications such as axises and regulating lines were the design elements which were chosen to fulfill the concepts. If the establishment of the architectural aim and design concepts, the process of selecting and constructing proper design elements, and the geometric application in the process are the design principles of the Doa-Rak-Dang block, the principles can be summarized as the geometric applications of axises and regulating lines interacting as the standard of the extension of public area.

Hypermethylation-mediated silencing of NDRG4 promotes pancreatic ductal adenocarcinoma by regulating mitochondrial function

  • Shi, Hao-Hong;Liu, Hai-E;Luo, Xing-Jing
    • BMB Reports
    • /
    • v.53 no.12
    • /
    • pp.658-663
    • /
    • 2020
  • The N-myc downstream regulated gene (NDRG) family members are dysregulated in several tumors. Functionally, NDRGs play an important role in the malignant progression of cancer cells. However, little is known about the potential implications of NDRG4 in pancreatic ductal adenocarcinoma (PDAC). The aim of the current study was to elucidate the expression pattern of NDRG4 in PDAC and evaluate its potential cellular biological effects. Here, we firstly report that epigenetic-mediated silencing of NDRG4 promotes PDAC by regulating mitochondrial function. Data mining demonstrated that NDRG4 was significantly down-regulated in PDAC tissues and cells. PDAC patients with low NDRG4 expression showed poor prognosis. Epigenetic regulation by DNA methylation was closely associated with NDRG4 down-regulation. NDRG4 overexpression dramatically suppressed PDAC cell growth and metastasis. Further functional analysis demonstrated that up-regulated NDRG4 in SW1990 and Canpan1 cells resulted in attenuated mitochondrial function, including reduced ATP production, decreased mitochondrial membrane potential, and increased fragmented mitochondria. However, opposite results were obtained for HPNE cells with NDRG4 knockdown. These results indicate that hypermethylation-driven silencing of NDRG4 can promote PDAC by regulating mitochondrial function and that NDRG4 could be as a potential biomarker for PDAC patients.

Multiple Facets of Sox Gene (SOX 유전자의 다양성)

  • 홍경원;김희수
    • Journal of Life Science
    • /
    • v.14 no.4
    • /
    • pp.716-725
    • /
    • 2004
  • Sox protein family, a transcription factor, has been found in whole animal kingdom, and contains a sequence-specific DNA binding domain called high mobility group domain (HMG). The Sox protein family based on the amino acid sequence of HMG domain was classified into 10 groups. Each group of Sox family shows significant conservation from nematode to human. The HMG domain affect to various developmental cell differentiation through binding to enhancer and regulating other transcription factors. Recently, many molecular biologists focus their research on the illustration of Sox-related disease, evolution and phylogeny. Especially, stem cell research with Sox gene family is indispensable field for understanding of their biological functions. The understanding of Sox genes may contribute to understand their role in human genetic disease and whole animal evolution.

A Comparative Study on the Laws regulating Multi-family Housing Amenities for Single or 2 resident Household in Korea, Japan and UK (1-2인 가구를 위한 공동주택의 공용공간 규정에 관한 한국·일본·영국의 건축법규 비교 연구)

  • Lee, Eunjoo;Lee, Sang Ho
    • Journal of the Korean housing association
    • /
    • v.26 no.5
    • /
    • pp.105-112
    • /
    • 2015
  • This research was aimed at finding clues of improving residential quality of the Urbanistic Housing which was introduced for the small household of 1-2 residents. It was the laws on communal amenity in multi-family housing that this research concentrated on. Looking into the multi-family housing standards for small household of Korea, Japan and UK, Japanese One-room housing Ordinance of Tokyo-do laid stress on avoiding conflict among residents and getting people mixed together. And UK's concentrated on every individual rooms inside HMO and suggested certain level of qualified life through the careful standards. On the other hand, Korea's just suggested minimum housing with unit households and nearly no amenity except for parking lots. There should be more than a physical space with some area which satisfies basic physiological needs in a residence. To become a quality residence filled with relationship, it is necessary that Urbanistic Housing are also required to provide communal amenities, not as much as regular housing for regular household but much more than Quasi-housing, the minimum residence. And it should be ensured by the legal system to make it more effective.

Sirtuin/Sir2 Phylogeny, Evolutionary Considerations and Structural Conservation

  • Greiss, Sebastian;Gartner, Anton
    • Molecules and Cells
    • /
    • v.28 no.5
    • /
    • pp.407-415
    • /
    • 2009
  • The sirtuins are a protein family named after the first identified member, S. cerevisiae Sir2p. Sirtuins are protein deacetylases whose activity is dependent on $NAD^+$ as a cosubstrate. They are structurally defined by two central domains that together form a highly conserved catalytic center, which catalyzes the transfer of an acetyl moiety from acetyllysine to $NAD^+$, yielding nicotinamide, the unique metabolite O-acetyl-ADP-ribose and deacetylated lysine. One or more sirtuins are present in virtually all species from bacteria to mammals. Here we describe a phylogenetic analysis of sirtuins. Based on their phylogenetic relationship, sirtuins can be grouped into over a dozen classes and subclasses. Humans, like most vertebrates, have seven sirtuins: SIRT1-SIRT7. These function in diverse cellular pathways, regulating transcriptional repression, aging, metabolism, DNA damage responses and apoptosis. We show that these seven sirtuins arose early during animal evolution. Conserved residues cluster around the catalytic center of known sirtuin family members.