• Biomolecules & Therapeutics
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• 제27권5호
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• pp.423-434
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• 2019

HSP90 is a molecular chaperone that increases the stability of client proteins. Cancer cells show higher HSP90 expression than normal cells because many client proteins play an important role in the growth and survival of cancer cells. HSP90 inhibitors mainly bind to the ATP binding site of HSP90 and inhibit HSP90 activity, and these inhibitors can be distinguished as ansamycin and non-ansamycin depending on the structure. In addition, the histone deacetylase inhibitors inhibit the activity of HSP90 through acetylation of HSP90. These HSP90 inhibitors have undergone or are undergoing clinical trials for the treatment of cancer. On the other hand, recent studies have reported that various reagents induce cleavage of HSP90, resulting in reduced HSP90 client proteins and growth suppression in cancer cells. Cleavage of HSP90 can be divided into enzymatic cleavage and non-enzymatic cleavage. Therefore, reagents inducing cleavage of HSP90 can be classified as another class of HSP90 inhibitors. We discuss that the cleavage of HSP90 can be another mechanism in the cancer treatment by HSP90 inhibition.

• 한국양식학회지
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• 제19권4호
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• pp.315-322
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• 2006

본 연구에서는 담수사육 감성돔을 대상으로 수온을 상승시켰을 때, 세포적 스트레스 측면에서 HSP90 및 HSP70 mRNA의 발현 정도를, 신경-내분비적 스트레스 측면에서 혈장 cortisol 및 glucose 농도를 조사하였다. RT-PCR법을 이용하여 생식소로부터 HSP90 (891 bp) 및 HSP70 (465 bp) cDNA 단편을 클로닝 하여, 타 종과 그 상동성을 비교해 본 결과, 감성돔 HSP90은 참돔 HSP90과 99%, 무지개송어 HSP90과 95%, 대서양 연어HSP90과 94%, zebrafish HSP90과 94%로 나타났으며, 감성돔 HSP70은 무지개송어 HSP70과 96%, silver seabream HSP70과 95%, zebrafish HSP70과 95%의 상동성을 나타내었다. 감성돔의 사육수온을 $30\;^{\circ}C$로 상승시켰을 때, HSP90 mRNA는 모든 조직에서 그 발현 정도가 $20\;^{\circ}C$ 실험구에 비하여 $7{\sim}9$배 정도 높았으나, HSP70 mRNA는 생식소에서만 발현하는 것으로 나타났다. 혈장 cortisol 및 glucose 농도는 $20\;^{\circ}C$ 실험구에 비하여 $30\;^{\circ}C$ 실험구에서 유의하게 증가한 것으로 나타났다.

• Asian-Australasian Journal of Animal Sciences
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• 제16권9호
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• pp.1261-1267
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• 2003

We have investigated whether HspBP1, a Hsp70 binding protein, could have effect on the assembly of the bovine progesterone receptor (bPR) with a chaperone complex consisting of bovine Hsp90 (bHsp90), bovine Hsp70 (bHsp70), Hop, Ydj-1, and p23. The bPR, isolated in its native conformation, loses its function to interact with progesterone hormone in the absence of this protein complex. However, in the presence of bHsp90, bHsp70, Hop, p23 and Ydj-1, its function could be restored in vitro. Our findings here indicate that the inclusion of HspBP1 to five-protein system prevented the proper assembly of progesterone receptor-chaperone complex and induce the loss of bPR ability to interact with hormone. Immunoprecipitation assays of bPR with HspBP1 show that the presence of HspBP1 did not have any effect on the assembly of Ydj-1 and bHsp70 with the progesterone receptor. However, further assembly of Hsp90, Hop and p23 was completely prevented and the function of the bPR was lost. In vitro competition and protein folding assays indicated that the binding of HspBP1 to bHsp70 prevented the ternary complex formation of bHsp70, bHsp90, and Hop. These results indicate that HspBP1 is a negative regulator of the assembly of Hsp90, Hop and Hsp70, and thus, prevent the proper maturation of unliganded bPR with chaperones assembly system.

• BMB Reports
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• 제42권10호
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• pp.623-630
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• 2009

Hsp90, an evolutionarily conserved molecular chaperone, is involved in the folding, stabilization, activation, and assembly of a wide range of 'client' proteins, thus playing a central role in many biological processes. Especially, several oncoproteins act as Hsp90 client proteins and tumor cells require higher Hsp90 activity than normal cells to maintain their malignancy. For this reason, Hsp90 has emerged as a promising target for anti-cancer drug development. It is still largely unknown how Hsp90 can recognize structurally unrelated client proteins. However, recent progress in structural studies on Hsp90 and its interaction with various co-chaperones has broadened our knowledge of how the Hsp90 ATPase activity, which is essential for its chaperone function, is regulated and coupled with the conformational changes of Hsp90 dimer. This review focuses on the roles of various Hsp90 co-chaperones in the regulation of the Hsp90 ATPase cycle, as well as in the selection of client proteins. In addition, the current development of Hsp90 inhibitors based on the structural information will be discussed.

• 생명과학회지
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• 제26권7호
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• pp.826-834
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• 2016

본 연구는 Hsp90 inhibitor 및 SIRT1 inhibitor의 병용처리가 항암제 다제내성(MDR) 인간 암세포의 증식 억제에 효과적임을 밝혔다. SIRT1 활성 억제가 Hsp90 inhibitor인 17-AAG의 세포 독성의 효과를 증강시켰으며, 이로 인해 Hsp90 inhibitors에 대한 내성을 극복시킬 수 있음을 인간 자궁암세포인 HeyA8의 MDR 변이주인 HeyA8- MDR 세포에서 확인하였다. SIRT1 inhibitor는 Hsp90 inhibitor에 의한 Hsp90 샤페론 기능 억제를 증강시키며, ubiquitin ligase CHIP의 발현 증강을 유발하여, Hsp90 client protein 인 mutant p53 (mut p53)의 분해를 촉진시킨다. Mut p53 의 발현 감소는 암세포의 Hsp90 inhibitor 내성 획득의 가장 중요한 원인으로 지적되는 heat shock factor 1 (HSF1)/heat shock proteins (Hsps)의 발현 억제와 관련됨을 알 수 있었으며, 이는 항암제 다제내성 세포에서 SIRT1 inhibitor에 의하여 Hsp90 inhibitor에 대한 감수성이 증강되는 분자적 기전임을 밝혔다. 그러므로, SIRT1 억제에 의한 mut p53/HSF1 발현 감소가 MDR 암세포의 Hsp90 inhibitors 내성 극복에 매우 유효함을 시사하는 결과를 얻었다.

• Fisheries and Aquatic Sciences
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• 제2권1호
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• pp.85-92
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• 1999

We examined the expression patterns of heat shock proteins in primary cultured hepatocytes from flounder (Paralichthys olivaceus) exposed to heat shock. The expression of hsp90, hsp70, hsp40, hsp30, and hsp27 was induced and major polypeptides were hsp70, hsp30 and hsp27. Northern blot analysis showed that expression of hsp70 was inhibited by transcriptional inhibitor actinomycin D, suggesting that expression of hsp70 gene is regulated at the transcriptional level. Prolonged exposure of cells to an elevated incubation temperature $(30^{\circ}C)$ induced the transient synthesis of hsp90, hsp70, hsp40, and hsp30 whereas maintenance of cells at a slightly higher incubation temperature $(32^{\circ}C)$ induced the continuous syntheses of these hsps. When cells were incubated at a higher temperatures $(35^{\circ}C\;or\;37^{\circ}C)$, the synthesis of hsps was almost similar to that of hsps in cells exposed to 32't except for the induction of hsp27 synthesis. These results that temperature and incubation time for optimum expression of each hsp during prolonged heat shock are different.

• 대한임상검사과학회지
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• 제49권4호
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• pp.460-469
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• 2017

열충격 단백질(heat shock proteins, HSPs)은 다양한 종양에서 과발현 되고, 종양이 형성되는 과정이나 그 예후에 영향을 주며, 분자량에 따라 HSP27, HSP60, HSP90, HSP100 등으로 구분한다. Heat shock protein90은 세포 내 불안정한 단백질을 보호하는 역할을 통해 질병의 유지에 기여하는데, 정상 조직에 비해 종양 세포에서 높은 수준으로 발현된다고 보고되었다. 이에 본 연구에서는 우리나라 사망원인 1위인 폐암 중 비소세포 폐암에서 Heat shock protein90 family 발현과 비소세포 폐암환자의 임상적 특징과의 상관관계를 분석하여 종양의 생물학적 표지자로서의 가능성을 조사하였다. HSP90 family의 발현과 임상병리학적 특성 및 생존율과의 상관관계를 분석한 결과 $HSP90{\alpha}$는 림프혈관강 침윤이 되지 않은 환자에서 높은 발현을 보였고(p=0.014), $HSP90{\beta}$ 은 조직학적 형태에서 편평상피세포 암종에서 높은 발현을 보였으며(p=0.003), GRP94 은 분화도가 낮을수록 높은 발현을 나타내었다(p=0.048). 생존율은 $HSP90{\alpha}$, $HSP90{\beta}$, GRP94 모두 발현 차이에 대한 유의성이 없었다. 본 연구를 통해 miRNA-126, miRNA-155, miRNA-200c의 발현은 비소세포 폐암의 진단을 위한 생물학적 표지자 및 예후 인자로서 사용될 수 있을 것으로 사료된다. 그리고 비소세포 폐암의 치료용으로 HSP90 family가 고려되어야 할 것이며, GRP94가 종양의 예후예측을 위한 중요한 인자라 사료된다.

• Nuclear Engineering and Technology
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• 제38권3호
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• pp.285-292
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• 2006

Thermoresistant (TR) clones of radiation-induced fibrosarcoma (RIF) cells have been reported to show an adaptive response to 1cGy of low dose radiation, and HSP25 and inducible HSP70 are involved in this process. In this study, to further elucidate the mechanism by which HSP25 and inducible HSP70 regulate the adaptive response, HSP25 or inducible HSP70 overexpressed RIF cells were irradiated with 1cGy and the cell cycle was analyzed. HSP25 or inducible HSP70 overexpressed cells together with TR cells showed increased G1 phase after 1cGy irradiation, while RIF cells did not. $[^3H]-Thymidine$ and BrdU incorporation also indicated that both HSP25 and inducible HSP70 are involved in G1 arrest after 1cGy irradiation. Molecular analysis revealed upregulation of p27Cip/Kip protein in HSP25 and inducible HSP70 overexpressed cells, and cotransfection of p27Cip/Kip antisense abolished the induction of the adaptive response and 1cGy-mediated G1 arrest. The above results indicate that induction of an adaptive response by HSP25 and inducible HSP70 is mediated by upregulation of p27Cip/Kip protein, resulting in low dose radiation-induced G1 arrest.

• International Journal of Industrial Entomology and Biomaterials
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• 제16권1호
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• pp.21-27
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• 2008

The expression of heat shock protein genes (Hsp 70, Hsp 40, Hsp 20.8 and Hsp 20.4) against thermal stress in silkworm Bombyx mori was performed through semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Upon exposure of silkworm to two temperature regimes ($38^{\circ}C$ and $42^{\circ}C$), significant change in the expression of Hsp gene was observed as compared to the control. Hsp 70 and Hsp 40 showed increased expression than the small heat shock protein genes Hsp 20.8 and Hsp 20.4. The Hsp 70 showed increased expression during the recovery period as compared to 1 hr thermal treatments ($38^{\circ}C$/1 hr and $42^{\circ}C$/1 hr). Whereas, Hsp 40, Hsp 20.8 and Hsp 20.4 genes showed higher expression level at initial stages that later gradually decrease during recovery period. Tissue specific expression of Hsp 70 showed variation in the level of expression amongst the tissues. The mid gut and fat body tissues showed higher expression than the cuticle and silk gland tissue. The Hsp 70, Hsp 40 gene expression was analyzed in thermotolerant (Nistari) and thermo susceptible silk worm strain (NB4D2) and results showed significant variation in their expression level. The Nistari showed higher expression of Hsp 70 and Hsp 40 genes than the NB4D2. These findings provide a better understanding of cellular protection mechanisms against environmental stress such as heat shock, as these Hsps are involved in an organism thermotolerance.

• 한국해양생명과학회지
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• 제5권2호
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• pp.92-98
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• 2020

Heat shock proteins (HSPs) are highly conserved cellular proteins that contribute to adaptive responses of organisms to a variety of stressors. In response to stressors, cellular levels of HSPs are increased and play critical roles in protein stability, folding and molecular trafficking. The mRNA expression pattern of two well-known heat shock protein transcripts, HSP70 and HSP90 were studied in two tissues of nerve ganglia, cerebral ganglion and pleuropedal ganglion of Pacific abalone (Haliotis discus hannai). It was observed that both HSP70 and HSP90 transcripts were upregulated under heat stress in both ganglion tissues. Expression level of HSP70 was found higher than HSP90 in both ganglia whereas cerebral ganglion showed higher expression than pleuropedal ganglion. The HSP70 and HSP90 showed higher expression at Day-1 after exposed to heat stress, later decreased at Day-3 and Day-7 onwards. The present result suggested that HSP70 and HSP90 synthesize in nerve ganglion tissues and may provide efficient protection from stress.