Biomedical subjects

Cheolho Cheong

Publications and source records attributed to Cheolho Cheong.

10 recordsLinked to original sources

PubMed2007

Differential antigen processing by dendritic cell subsets in vivo.

Dendritic cells (DCs) process and present self and foreign antigens to induce tolerance or immunity. In vitro models suggest that induction of immunity is controlled by regulating the presentation of antigen, but little is known about how DCs control antigen presentation in vivo. To examine antigen processing and presentation in vivo, we specifically targeted antigens to two major subsets of DCs by using chimeric monoclonal antibodies. Unlike CD8+ DCs that express the cell surface protein CD205, CD8- DCs, which are positive for the 33D1 antigen, are specialized for presentation on major histocompatibility complex (MHC) class II. This difference in antigen processing is intrinsic to the DC subsets and is associated with increased expression of proteins involved in MHC processing.

Amino Acid Sequence↗

PubMed2006

Role of INK4a locus in normal eye development and cataract genesis.

The murine INK4a locus encodes the critical tumor suppressor proteins, p16(INK4a) and p19(ARF). Mice lacking both p16(INK4a) and p19(ARF) (INK4a-/-) in their FVB/NJ genetic backgrounds developed cataracts and microophthalmia. Histopathologically, INK4a-/- mice showed defects in the developmental regression of the hyaloid vascular system (HVS), retinal dysplasia, and cataracts with numerous vacuolations, closely resembling human persistent hyperplastic primary vitreous (PHPV). Ocular defects, such as retinal fold and abnormal migration of lens fiber cells, were observed as early as embryonic day (E) 15.5, thereby resulting in the abnormal differentiation of the lens. We also found that ectopic expression of p16(INK4a) resulted in the induction of gammaF-crystallin, suggesting an important role of INK4a locus during mouse eye development, and also providing insights into the potential genetic basis of human cataract genesis.

Animals↗

PubMed2006

A dominant complement fixation pathway for pneumococcal polysaccharides initiated by SIGN-R1 interacting with C1q.

The intricate system of serum complement proteins provides resistance to infection. A pivotal step in the complement pathway is the assembly of a C3 convertase, which digests the C3 complement component to form microbial binding C3 fragments recognized by leukocytes. The spleen and C3 provide resistance against blood-borne S. pneumoniae infection. To better understand the mechanisms involved, we studied SIGN-R1, a lectin that captures microbial polysaccharides in spleen. Surprisingly, conditional SIGN-R1 knockout mice developed deficits in C3 catabolism when given S. pneumoniae or its capsular polysaccharide intravenously. There were marked reductions in proteolysis of serum C3, deposition of C3 on organisms within SIGN-R1(+) spleen macrophages, and formation of C3 ligands. We found that SIGN-R1 directly bound the complement C1 subcomponent, C1q, and assembled a C3 convertase, but without the traditional requirement for either antibody or factor B. The transmembrane lectin SIGN-R1 therefore contributes to innate resistance by an unusual C3 activation pathway.

Animals↗

PubMed2005

The pleiotropy of telomerase against cell death.

The end of eukaryotic genomic DNA is capped by a specialized structure called as "telomere", which consists of the repetitive array of nucleotide sequence, TTAGGG, in humans and mice, and a variety of binding proteins. Telomerase is a ribonucleoprotein (RNP) complex responsible for the elongation of telomeres to maintain the genomic integrity, and is composed of telomerase reverse transcriptase (TERT), telomerase RNA component (TERC), and their associated factors regulating the catalytic activity of telomerase. Although it is now apparent that telomerase protects cells from apoptosis via the maintenance of genomic integrity by stabilizing telomeres, our understanding for the physiological role of telomerase is yet far from completion, and emerging evidence suggests that telomerase has additional extratelomeric roles in mediating cell survival and anti-apoptotic functions against various cytotoxic stresses. Here we summarize and discuss how telomerase and telomeres are involved in mediating cellular protection against apoptosis.

Animals↗

PubMed2005

Dynamic rearrangement of telomeres during spermatogenesis in mice.

Chromosomal structure within the nucleus influences various biological processes such as transcription and replication. Telomeres are located at the end of eukaryotic chromosomes and they can be a decisive factor for correct chromosomal positioning. To gain new insight into telomere dynamics, we examined telomere length and positional changes during spermatogenesis using improved fluorescence in situ hybridization (FISH) and in situ telomeric repeat amplification protocols (TRAP) on histological sections. FISH revealed telomere length and chromosome position within nuclei change dynamically. Telomere extension occurred during spermiogenesis. In situ TRAP analysis verified elevated telomerase activity in elongating spermatids. Together, these data show that elongated spermatids have longer telomeres than precursor spermatogenic cells. This observation indicates that telomere elongation in haploid cells occurs after meiosis and in the absence of genomic replication. Analyses of testes from telomerase null mice further support the significance of telomere dynamics during spermatogenesis and the existence of an alternative telomere extension pathway.

Animals↗

PubMed2005

Generation of reversible Rb-knockdown mice.

This study describes the generation of reversible Rb-knockdown mice using Tet-off system coupled with Rb-deficient mice currently available. Mice expressing pRB conditionally in Rb-/- background were generated by crossings P(hCMV)-tTA/TRE-Rb transgenic mice with conventional Rb+/- mice. Transgenic Rb was tightly controlled with reversibility and biologically effective as exemplified by cyclin E expression in a doxycycline-dependent manner in mouse embryonic fibroblasts. However, its ectopic expression was not sufficient to rescue the phenotypes of Rb-/- embryos at organismal level, suggesting the requirement of more sophisticated regulation of pRB. With all, these results demonstrate that our experimental strategy can be an alternative way to convert classical gene-disrupted mice into reversible conditional ones.

Animals↗

PubMed2005

Extratelomeric functions of telomerase.

Telomerase reverse transcriptase (TERT), a catalytic subunit of telomerase, has been demonstrated to exert a reverse transcriptase function when combined with telomerase RNA component (TERC), the complex of which ensures the maintenance of telomere length in all eukaryotes. Telomerase also prevents cell death, and promotes survival in many types of cells, from various tissues or organs including neurons, muscle, and immune cells, as well as a variety of tumor cells. Recently, a new aspect of telomerase activity, independent of telomere lengthening, has emerged to explain its protective effects on cell survival. Consistent with this, TERT was found to enhance tumorigenesis, and to regulate the expression of genes that control cell growth, which cannot be explained by telomere stabilization per se. Furthermore, the observation that TERT resides not only in the nucleus, but also in the cytosol, reinforces the notion of possible telomere-independent functions. In this review, recent studies regarding the extratelomeric functions of TERT have been comprehensively summarized, and their implications discussed.

Animals↗

PubMed2003

Mouse models for telomere and telomerase biology.

Telomeres serve a critical role in maintenance of genomic stability in all eukaryotes, from yeast to human. The maintenance of telomeres is achieved by the telomerase complex, which is largely composed of telomerase reverse transcriptase (TERT) and telomerase RNA component (TERC). A variety of mouse models have provided valuable insights into the relationship between the telomerase complex and telomere dysfunction at the organismal level and helped understand their biological significance in human. Recently, in addition to its role in maintenance of the telomeres, novel functions of the telomerase complex have been emerging. In this review, studies of all gene-targeted or transgenic mouse models so far generated for telomerase and telomere biology are comprehensively described, and potential novel functions of telomerase are briefly discussed.

Animals↗

PubMed2002

Multiple developmental defects derived from impaired recruitment of ASC-2 to nuclear receptors in mice: implication for posterior lenticonus with cataract.

ASC-2, a recently isolated transcriptional coactivator molecule, stimulates transactivation by multiple transcription factors, including nuclear receptors. We generated a potent dominant negative fragment of ASC-2, encompassing the N-terminal LXXLL motif that binds a broad range of nuclear receptors. This fragment, termed DN1, specifically inhibited endogenous ASC-2 from binding these receptors in vivo, whereas DN1/m, in which the LXXLL motif was mutated to LXXAA to abolish the receptor interactions, was inert. Interestingly, DN1 transgenic mice but not DN1/m transgenic mice exhibited severe microphthalmia and posterior lenticonus with cataract as well as a variety of pathophysiological phenotypes in many other organs. Our results provide a novel insight into the molecular and histopathological mechanism of posterior lenticonus with cataract and attest to the importance of ASC-2 as a pivotal transcriptional coactivator of nuclear receptors in vivo.

Amino Acid Motifs↗

PubMedDate not supplied

Hematopoietic malignancies associated with increased Stat5 and Bcl-x(L) expressions in Ink4a/Arf-deficient mice.

The INK4a/ARF locus, which encodes the two distinct proteins p16(INK4a) and p14(ARF), is frequently altered in various hematological malignancies as well as in other types of cancers in humans. In this study, we surveyed tumors that had spontaneously developed in Ink4a/Arf-deficient mice with an inbred FVB/NJ genetic background. We found that an Ink4a/Arf-deficiency exerted more severe effects on the induction of hematopoietic malignancies in mice with an inbred FVB/NJ genetic background than in mice with a mixed genetic background. We also provided the evidence that this prevalence of hematopoietic malignancies in Ink4a/Arf-deficient mice is associated with the upregulated expressions of Stat5 and its transcriptional target, Bcl-x(L), both of which are involved in the regulation of hematopoiesis. These results suggest a possible implication of the Ink4a/Arf locus in the control of hematopoietic pathways by negatively regulating the Stat5-signalling pathways.

Animals↗