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The Alpha Subunit of Go Interacts with Promyelocytic Leukemia Zinc Finger Protein
Sung-Ho Ghil 대한의생명과학회 2004 Biomedical Science Letters Vol.10 No.4
Heterotrimeric GTP binding proteins (G proteins) transduce signals of a variety of hormones and neurotransmitters. Go is one of the most abundant G proteins in the brain and classified as the Gi/Go family due to their sequence homology to Gi proteins. While the Gi proteins inhibit adenylyl cyclase and decrease the intracellular cAMP concentration, the functions of Go is not clearly understood despite their sequence homology to Gi. The promeylocytic leukemia zinc finger protein (PLZF) is a DNA binding transcription factor and is expressed highly in central nervous system (CNS). Several studies reported that PLZF may be involved in regulation segmentation/differentiation during CNS development. Here, I report that the alpha subunit of Go (Goα) interacts with PLZF. The interaction between Goα and PLZF was verified by using GST pulldown assay and co-immunoprecipitation. Our findings indicate that Goα could modulate gene expression via interaction with PLZF during neuronal or brain development.
The Alpha Subunit of Go Interacts with Promyelocytic Leukemia Zinc Finger Protein
Ghil Sung-Ho 대한의생명과학회 2004 Biomedical Science Letters Vol.10 No.4
Heterotrimeric GTP binding proteins (G proteins) transduce signals of a variety of hormones and neurotransmitters. Go is one of the most abundant G proteins in the brain and classified as the Gi/Go family due to their sequence homology to Gi proteins. While the Gi proteins inhibit adenylyl cyclase and decrease the intracellular cAMP concentration, the functions of Go is not clearly understood despite their sequence homology to Gi. The promeylocytic leukemia zinc finger protein (PLZF) is a DNA binding transcription factor and is expressed highly in central nervous system (CNS). Several studies reported that PLZF may be involved in regulation segmentation/differentiation during CNS development. Here, I report that the alpha subunit of Go (Go ) interacts with PLZF. The interaction between Goa and PLZF was verified by using GST pulldown assay and co-immunoprecipitation. Our findings indicate that Goa could modulate gene expression via interaction with PLZF during neuronal or brain development.
Goα를 영구적으로 발현하는 세포에서의 신경돌기 성장 억제
길성호(Sung-Ho Ghil),서해영(Haeyoung Suh-Kim) 대한해부학회 2002 Anatomy & Cell Biology Vol.35 No.2
G 단백질은 신경전달물질과 호르몬에 의해서 발생되는 신호를 세포내부로 중개하는 신호전달물질이다. G 단백질 중 Go 는 뇌조직의 막에 상당량 발현되는 단백질이지만, 아직까지 그 기능이 정확히 알려져 있지 않다. 본 연구팀은 선행연구에서 Go의 α 소단위체인 αo를 신경모세포종인 F11세포에 일시적으로 과발현시키면, 신경돌기의 형성에 큰 영향이 있음을 보고한바 있다. 본 연구에서는 이러한 변화가 유전자의 일시적 과발현에 의해서 생기는 비특이 적 현상인지, 아니면 αo에 의해서 일어나는 특이적 현상인지를 규명하기 위하여 F11 세포에 αo를 영구적으로 발현하는 세포를 제작한 후, αo가 지속적으로 발현될 때 신경세포의 분화과정에서의 변화를 조사하였다. αo의 야생형과 돌연변이형을 지속적으로 발현하는 F11 세포를 모두 제작하였다. 각 세포에 dibutyryl cAMP를 처리한 후 신경돌기의 길이를 측정하였다. 정상적인 F11 세포의 경우, 신경돌기의 길이는 57.9±7.0 μm이었으며, 야생형과 돌연변이 αo가 지속적으로 발현된 세포의 경우, 신경돌기의 길이는 각각 34.4±5.1 μm와 30.5±3.6 μm이었다. 이는 정상 F11 세포에 비하여 각각 40.6%, 47.3% 감소한 것으로서, αo가 지속적으로 발현되는 경우에, 일시 과발현되는 경우와 마찬가지로 신경세포의 분화과정 중 특히 신경돌기의 형성과정을 조절한다는 사실을 의미한다. 나아가 두 가지 다른 접근법에 의하여 동일한 결과를 얻었으므로 신경돌기 형성과정의 변화는 αo에 특이적으로 일어남을 알 수 있었다. Heterotrimeric G proteins mediate signals generated by neurotransmitters and hormones. Among G proteins, Go is found in a large quantity in brain and growth cone membranes of neurons. In spite of its abundance in neurons, the role of Go is not fully understood. In the previous study, we showed that transient expression of the α subunit of Go (αo) modulated neurite outgrowth in F11 cells. It is possible that transient transfection may cause transient accumulation of the protein, which itself may alter differentiation process in non-specific manner. In this study, we determined that modulation of neurite outgrowth by αo was specific by evaluating the effect of αo in stably transformed F11 cells. F11 cells stably expressing the wild type αo (αowt) and a constitutively active form of αo (αoQ205L) were established. In normal F11 cells and αo-stable cell lines, the neurite length was measured in the presence of dibutyryl cAMP. In normal F11 cells, the average length of neurites was 57.9±7.0 μm. In αowt- and αoQ205L-expressing cells, the average length were 34.4±5.1 μm 30.5±3.6 μm, respectively. Thus, stable expression of αowt and αoQ205L caused a decrease in neurite outgrowth by 40.6%, 47.3% respectively. This result indicates that modulation of neurite by αo was specific to the function of αo but not due to accumulation of exogenous proteins.
( Ghil Suk Yoon ),( Yang Kyu Choi ),( Ha Na Bak ),( Beom Joon Kim ),( Myeung Nam Kim ),( Je Ne Choi ),( Hye Myung Rheu ),( Joo Ryung Huh ),( Jee Ho Choi ),( Sung Eun Chang ) 대한피부과학회 2009 Annals of Dermatology Vol.21 No.1
Background: Angioimmunoblastic T-cell lymphoma (AITL) is a complex lymphoproliferative disorder and often mimics a viral infection with frequent skin involvement. Epstein-Barr virus (EBV) and human herpes virus (HHV)-6 are reported to be associated with AITL, but there are conflicting results. Objective: We evaluated the association of EBV and HHV-6 with AITL. Methods: We reviewed the clinical, histological and immunophenotypical features of 19 cases of AITL. Among them, 11 lymph node biopsies of AITL were examined for HHV-6, -7, and -8 by polymerase chain reaction (PCR) using virus-specific primers. In situ hybridization of EBV early region RNA (EBER) was performed and T cell receptor (TCR) gene rearrangement was also investigated in some cases. Results: Among these 19 cases, maculopapular, plaque or nodular skin lesions accompanied AITL in 12 cases. Clonal TCR gene rearrangement was seen in 8/9 cases tested. EBER in situ hybridization was positive in 8 cases (57.1%). Among 7 cases with skin biopsies, five cases were consistent with cutaneous involvement of AITL, 1 case was a drug eruption, and the other case was Kaposi`s sarcoma. Except a HHV-8 (+) case who also had Kaposi`s sarcoma, all of these cases were negative for HHV-6, -7 and -8. Conclusion: Skin manifestation seems to be a cardinal component of AITL, be it in the context of presentation, progression or recurrent disease. Recognition of clinicopathological features of skin lesions in AITL as diagnostic clues should be stressed among dermatologists. The lack of HHV-6, -7 and -8 in lymph node biopsy of AITL argues against a pathogenic role for HHVs in AITL. (Ann Dermatol(Seoul) 21(1) 1∼5, 2009)
Effect of Cyclosporine on Peripheral Blood and Lesional Skin in Psoriatic Patients
( Sung Eun Chang ),( Woo Jin Yun ),( Ghil Suk Yoon ),( Jee Ho Choi ),( Bong Seong Kim ),( Soo Jong Hong ) 대한피부과학회 2007 Annals of Dermatology Vol.19 No.3
Background: Cyclosporine effectively suppresses immune responses and inhibits skin homing T cell responses in psoriasis. E-selectin is known to be up-regulated on vascular endothelium of inflammatory skin lesions such as psoriasis. Purpose: Based on our previous study that cyclosporine decreased lesional cutaneous lymphocyte antigen (CLA)+ T cells in psoriatic patients, we tried to find any change of CLA+ T cells in peripheral blood in psoriatic patients, since psoriasis is a disease of systemic T cell activation. Subjects and Methods: Peripheral blood of 8 patients with chronic plaque type psoriasis at 0, 3, 6, 12, 18 weeks after cyclosporine was examined by flow cytometry using anti-CLA antibody. Five skin biopsy samples at 0, 3, 6, 12, 18 weeks were immunohistochemically stained with anti E-selectin antibody. Results: Our results demonstrate that the number of CD3+ CLA+ and CD4+CLA+ T cells was significantly reduced in the peripheral blood at week 3, but gradually increased to the level of baseline at 18 weeks. In psoriatic skin lesions, with decrease of PASI score and CLA+ T cells number, the expression of E-selectin on the endothelial cells was gradually decreased throughout 18 weeks of therapy. Conclusion: These results suggest that cyclosporine suppresses the migration of skin homing T cells to psoriatic skin lesions, in part, through the inhibition of E-selectin on the endothelial cells. (Ann Dermatol (Seoul) 19(3) 106~111, 2007)