• BMB Reports
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• 제52권11호
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• pp.641-646
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• 2019

The Ron proto-oncogene is a human receptor for macrophage-stimulating protein (MSP). The exclusion of exon 11 in alternative splicing generates ${\Delta}RON$ protein that is constitutively activated. Heterogenous ribonucleaoprotein (hnRNP) $C_1/C_2$ is one of the most abundant proteins in cells. In this manuscript, we showed that both hnRNP $C_1$ and $C_2$ promoted exon 11 inclusion of Ron pre-mRNA and that hnRNP $C_1$ and hnRNP $C_2$ functioned independently but not cooperatively. Moreover, hnRNP $C_1$ stimulated exon 11 splicing through intron 10 activation but not through intron 11 splicing. Furthermore, we showed that, whereas the RRM domain was required for hnRNP $C_1$ function, the Asp/Glu domain was not. In conclusion, hnRNP $C_1/C_2$ promoted exon 11 splicing independently by stimulating intron 10 splicing through RRM but not through the Asp/Glu domain.

• 미생물학회지
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• 제54권2호
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• pp.91-97
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• 2018

진화적으로 보존된 TREX 복합체의 구성요소인 Yra1/ALY는 hnRNP-유사 단백질의 REF (RNA와 방출인자 결합단백질) 계열에 속하는 단백질로서 전사, 핵 RNA의 안정성, mRNA의 핵에서 방출 등 여러 과정에 관여하는 것으로 알려져 있다. 분열효모 Schizosaccharomyces pombe의 게놈에는 2개의 REF 단백질을 암호화하고 있다. 이미 mRNA 방출인자로 알려진 Mlo3 이외에 THO 복합체의 구성인자로 예측되는 Tho4이 존재한다. 본 연구에서 tho4 (SPBC106.12c) 유전자의 결실이 생장과 mRNA의 방출에 영향을 주지 않는다는 것을 알았다. 그러나 tho4 유전자를 과발현시키면 생장이 늦어지고 $poly(A)^+$ RNA가 핵 안에 약간 축적되었다. ${\Delta}tho4$ ${\Delta}mlo3$와 ${\Delta}tho4$ ${\Delta}mex67$ 이 중 돌연변이는 어느 것도 추가적인 생장 결함을 보이지 않았다. 또한 Yeast two-hybrid와 공동침전(Co-immunoprecipitation) 분석에서 Tho4는 THO/TREX 복합체의 다른 구성인자들과 어떠한 상호작용도 보이지 않았다. 이와 같은 관찰결과들은 S. pombe의 Tho4 단백질이 기대와는 다르게THO/TREX 복합체의 구성인자가 아니며, mRNA 방출에도 직접 관여하지 않음을 의미한다.

• BMB Reports
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• 제50권9호
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• pp.466-471
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• 2017

The results of this study show that c-Jun N-terminal kinase (JNK) activation was associated with the enhancement of docetaxel-induced cytotoxicity by simvastatin in DU145 human prostate cancer cells. To better understand the basic molecular mechanisms, we investigated simvastatin-regulated targets during simvastatin-induced cell death in DU145 cells using two-dimensional (2D) proteomic analysis. Thus, vimentin, Ras-related protein Rab-1B (RAB1B), cytoplasmic hydroxymethylglutaryl-CoA synthase (cHMGCS), thioredoxin domain-containing protein 5 (TXNDC5), heterogeneous nuclear ribonucleoprotein K (hnRNP K), N-myc downstream-regulated gene 1 (NDRG1), and isopentenyl-diphosphate Delta-isomerase 1 (IDI1) protein spots were identified as simvastatin-regulated targets involved in DU145 cell death signaling pathways. Moreover, the JNK inhibitor SP600125 significantly inhibited the upregulation of NDRG1 and IDI protein levels by combination treatment of docetaxel and simvastatin. These results suggest that NDRG1 and IDI could at least play an important role in DU145 cell death signaling as simvastatinregulated targets associated with JNK activation.