• 생명과학회지
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• 제14권4호
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• pp.716-725
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• 2004

Sox 패밀리는 동물계 전체에서 찾아지는 전사인자이고, HMG라는 특이적인 DNA결합 도메인을 가진다. 이 Sox 패밀리는 HMG 도메인의 아미노산 서열을 바탕으로 현재 10개의 그룹으로 분류된다. 각 그룹의 오소로그한 Sox 단백질들은 선충에서 인간까지 상당한 보존성을 보인다. HMG 도메인은 전사 촉진 좌위에 결합하고 다른 전사인자들의 결합을 조절함으로써 동물 발생과정의 다양한 세포에서 발현되어 그들의 분화에 결정적인 영향을 미친다. 최근 많은 분자 생물학자들이 Sox 유전자와 관련된 질병, 진화, 그리고 계통 분류 등에 많은 관심을 보이고 있다. 특히, 줄기세포에서 Sox 유전자의 연구는 그들의 생물학적인 기능을 이해하기 위해 꼭 필요한 분야이다. 아마도 이 Sox 유전자들을 이해함으로써, 인간의 유전적 질병과 인간을 포함한 전체 동물계의 진화를 이해할 수 있는 열쇠가 될 것이라 생각한다.

• 대한의생명과학회지
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• 제12권4호
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• pp.405-411
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• 2006

Heterotrimeric GTP binding proteins (G proteins) mediate signal transduction generated by neurotransmitter and hormones. Among G-proteins, Go is classified as a member of the Go/Gi family and the most abundant heterotrimeric G protein in brain. Most of the mechanistic analyses on the activation of Go indicated its action to be mediated by the $G{\beta}{\gamma}$ dimer because downstream effectors for its ${\alpha}$ subunit have not been clearly defined. To determine the downstream effectors of alpha subunits of Go ($Go{\alpha}$), we used yeast two-hybrid system to screen $Go{\alpha}$ interacting partners in cDNA library from the human brain. A brain specific high mobility group box containing protein (BHX), A possible transcription factor, was identified as a $Go{\alpha}$ interacting protein. We confirmed interaction between $Go{\alpha}$ and BHX employing in vitro affinity binding assay. Moreover, active form of $Go{\alpha}$ preferentially interacts with BHX than inactive farm. Our findings indicate that $Go{\alpha}$ could modulate gene expression via interaction with BHX during neuronal or brain development.

• Reproductive and Developmental Biology
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• 제32권4호
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• pp.211-215
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• 2008

The HMG box containing protein (HBP) has a high mobility group domain and involved in the regulation of proliferation and differentiation of tissues. We screened HBP2 in glioblastoma using Suppression Subtractive Hybridization (SSH) and isolated human spermatogonial stem cell-like cells (hSSC-like cells) derived from patients of nonobstructive azoospermia (NOA). Expression of HBP2 was analyzed by RT-PCR in undifferentiated stem cells (human Embryonic Stem Cells, hSSC-like cells 2P) and spontaneous differentiated stem cells (hSSC-like cells 4P). It was overexpressed in hESC and hSSC-like cells 2P but not in hSSC-like cells 4P. Also, the expression level of HBP2 was downregulated in colon tumor tissues compared to normal tissues. Specifically in synchronized WI-38 cells, HBP2 was highly upregulated until the G1 phase of the cell cycle and gradually decreased during the S phase. Our results suggest that HBP2 was downregulated during the spontaneous differentiation of hSSC-like cells. HBP2 was differently expressed in colon tissues and was related to G1-progression in WI-38 cells. It may playa role in the maintenance of an undifferentiated hSSC-like cell state and transits from G1 to S in WI-38 cells. This research was important that it identified a biomarker for an undifferentiated state of hSSC-like cells and characterized its involvement to arrest during cell cycle in colon cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제16권12호
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• pp.4981-4985
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• 2015

Background: Colorectal cancer (CRC) is a leading cause of morbidity and mortality worldwide. Targeting autophagic cell death is emerging as a novel strategy in cancer chemotherapy. Aldose reductase (AR) catalyzes the rate limiting step of the polyol pathway of glucose metabolism; besides reducing glucose to sorbitol, AR reduces lipid peroxidation-derived aldehydes and their glutathione conjugates. A complex interplay between autophagic cell death and/or survival may in turn govern tumor metastasis. This exploratory study aimed to investigate the potential role of AR inhibition using a novel inhibitor Fidarestat in the regulation of autophagy in CRC cells. Materials and Methods: For glucose depletion (GD), HT-29 and SW480 CRC cells were rinsed with glucose-free RPMI-1640, followed by incubation in GD medium +/- Fidarestat ($10{\mu}M$). Proteins were extracted by a RIPA-method followed by Western blotting ($35-50{\mu}g$ of protein; n=3). Results: Autophagic regulatory markers, primarily, microtubule associated protein light chain (LC) 3, autophagy-related gene (ATG) 5, ATG 7 and Beclin-1 were expressed in CRC cells; glyceraldehyde-3 phosphate dehydrogenase (GAPDH) was used as an internal reference. LC3 II (14 kDa) expression was relatively high compared to LC3A/B I levels in both CRC cell lines, suggesting occurrence of autophagy. Expression of non-autophagic markers, high mobility group box (HMG)-1 and Bcl-2, was comparatively low. Conclusions: GD +/- ARI induced autophagy in HT-29 and SW-480 cells, thereby implicating Fidarestat as a promising therapeutic agent for colorectal cancer; future studies with more potent ARIs are warranted to fully dissect the molecular regulatory networks for autophagy in colorectal carcinoma.

• Reproductive and Developmental Biology
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• 제29권2호
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• pp.63-68
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• 2005

Cloned calves derived from somatic cell nuclear transfer (SCNT) have been frequently lost by sudden death at 1 to 3 month following healthy birth. To address whether placental anomalies are responsible for the sudden death of cloned calves, we compared protein patterns of 2 placentae derived from SCNT of Korean Native calves died suddenly at two months after birth and those of 2 normal placentae obtained from AI fetuses. Placental proteins were separated using 2-Dimensional gel electrophoresis. Approximately 800 spots were detected in placental 2-D gel stained with coomassie-blue. Then, image analysis of Malanie III (Swiss Institute for Bioinformatics) was performed to detect variations in protein spots between normal and SCNT placentae. In the comparison of normal and SCNT samples, 8 spots were identified to be up-regulated proteins and 24 spots to be down-regulated proteins in SCNT placentae, among which proteins were high mobility group protein HMG1, apolipoprotein A-1 precursor, bactenecin 1, tropomyosin beta chain, $H^+-transporting$ ATPase, carbonic anhydrase II, peroxiredoxin 2, tyrosine-rich acidic matrix protein, serum albumin precursor and cathepsin D. These results suggested that the sudden death of cloned calves might be related to abnormal protein expression in placenta.