• Title/Summary/Keyword: and receptors

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CDK2AP1, a Cyclin-Dependent Kinase 2-Associated Protein, Interacts with Kinesin-1 through Kinesin Superfamily Protein 5A (KIF5A) (Cyclin-dependent kinase 1 결합 단백질 CDK2AP1은 kinesin superfamily protein 5A (KIF5A)을 매개로 Kinesin-1와 결합)

  • Myoung Hun Kim;Se Young Pyo;Young Joo Jeong;Sung Woo Park;Mi Kyoung Seo;Won Hee Lee;Sang-Hwa Urm;Mooseong Kim;Jung Goo Lee;Dae-Hyun Seog
    • Journal of Life Science
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    • v.33 no.7
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    • pp.531-537
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    • 2023
  • Intracellular and axonal transport is mediated by microtubule-dependent motor proteins, such as kinesins and cytoplasmic dynein. Kinesin moves along the microtubule to the positive end of the microtubule, while dynein moves to the negative end of the microtubule. Kinesin-1 was first identified as a kinesin superfamily protein (KIF) that functions in the intracellular transport of various cargoes, including organelles, neurotransmitter receptors, and mRNA-protein complexes, through interactions between the carboxyl (C)-terminal domain and the cargo. It interacts with other cargoes, but the adapter/scaffold proteins that mediate between kinesin-1 and the cargo have yet to be fully identified. In this study, a yeast two-hybrid screen was used to identify adapter proteins that interact with the C-terminal region of KIF5A. We found an association between the C-terminal region of KIF5A and the cyclin-dependent kinase 2-associated protein 1 (CDK2AP1), originally identified in malignant hamster oral keratinocytes. CDK2AP1 bound to the C-terminal region of KIF5A and did not interact with KIF3A (the motor of kinesin-2), KIF5B, KIF5C, and kinesin light chain 1 (KLC1). The C-terminal region of CDK2AP1 is essential for its interaction with KIF5A. When co-expressed in HEK-293T cells, CDK2AP1 and kinesin-1 co-immunoprecipitated and co-localized in the cells. These results suggest that the KIF5A-CDK2AP1 interaction serves as an adapter protein connecting kinesin-1 and the cargo when kinesin-1 transports cargo in cells.

Identifying sources of heavy metal contamination in stream sediments using machine learning classifiers (기계학습 분류모델을 이용한 하천퇴적물의 중금속 오염원 식별)

  • Min Jeong Ban;Sangwook Shin;Dong Hoon Lee;Jeong-Gyu Kim;Hosik Lee;Young Kim;Jeong-Hun Park;ShunHwa Lee;Seon-Young Kim;Joo-Hyon Kang
    • Journal of Wetlands Research
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    • v.25 no.4
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    • pp.306-314
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    • 2023
  • Stream sediments are an important component of water quality management because they are receptors of various pollutants such as heavy metals and organic matters emitted from upland sources and can be secondary pollution sources, adversely affecting water environment. To effectively manage the stream sediments, identification of primary sources of sediment contamination and source-associated control strategies will be required. We evaluated the performance of machine learning models in identifying primary sources of sediment contamination based on the physico-chemical properties of stream sediments. A total of 356 stream sediment data sets of 18 quality parameters including 10 heavy metal species(Cd, Cu, Pb, Ni, As, Zn, Cr, Hg, Li, and Al), 3 soil parameters(clay, silt, and sand fractions), and 5 water quality parameters(water content, loss on ignition, total organic carbon, total nitrogen, and total phosphorous) were collected near abandoned metal mines and industrial complexes across the four major river basins in Korea. Two machine learning algorithms, linear discriminant analysis (LDA) and support vector machine (SVM) classifiers were used to classify the sediments into four cases of different combinations of the sampling period and locations (i.e., mine in dry season, mine in wet season, industrial complex in dry season, and industrial complex in wet season). Both models showed good performance in the classification, with SVM outperformed LDA; the accuracy values of LDA and SVM were 79.5% and 88.1%, respectively. An SVM ensemble model was used for multi-label classification of the multiple contamination sources inlcuding landuses in the upland areas within 1 km radius from the sampling sites. The results showed that the multi-label classifier was comparable performance with sinlgle-label SVM in classifying mines and industrial complexes, but was less accurate in classifying dominant land uses (50~60%). The poor performance of the multi-label SVM is likely due to the overfitting caused by small data sets compared to the complexity of the model. A larger data set might increase the performance of the machine learning models in identifying contamination sources.

Pharmacological Action Mechanism(s) of Vasodilator Effect of Calcitonin Gene-related Peptide in Rat Basilar Arteries (흰쥐의 뇌 기저동맥에서 CGRP에 의한 혈관 이완반응의 기전에 대한 연구)

  • Rhim, Byung-Yong;Hong, Sun-Hwa;Kim, Chi-Dae;Lee, Won-Suk;Kim, Dong-Heon;Hong, Ki-Whan
    • The Korean Journal of Pharmacology
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    • v.32 no.1
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    • pp.39-49
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    • 1996
  • In the present study, we observed change in intracellular $Ca^{2+}$$([Ca^{2+}]_i)$ as measured with the fluorescent $Ca^{2+}-indicator$ fura-2 in association with force development of the rat basilar arteries during activation by$K^+$ depolarizing solution and U46619, a thromboxane analogue, in the absence and the presence of calcitonin-gent related peptide (CGRP). CGRP (30 and 100 nM) caused a concentration-dependent inhibition of U46619-induced contraction with decrease in $[Ca^{2+}]_i$, whereas it did not exert any effect on the $K^+$ (90 mM)-induced contraction and increase in $[Ca^{2+}]_i$, Further, $[Ca^{2+}]_i-force$ relationships were determined by plotting the ratio of $F_{340}/F_{380}$ $([Ca^{2+}]_i)$ as a function of the force induced by U46619, and the results were compared with those obtained in the presence of CGRP. The curves obtained in the presence of CGRP (30 and 100 nM) were significantly moved to downward without right shift of the curves suggesting that CGRP inhibited the U46619-induced contraction only by mediation of reduction in $[Ca^{2+}]_i$ with out any change in the sensitivity of contractile apparatus to $Ca^{2+}$. The CGRP-induced attenuation of $[Ca^{2+}]_i$ and force development was significantly inhibited under pretreatment with CGRP $(8{\sim}37)$ fragment (100 nM), a CGRP1 receptor antagonist. Both the reduced contraction and reduction in $[Ca^{2+}]_i$ caused by CGRP were fully reversed by pretreatment with charybdotoxin (100 nM) and iberiotoxin (100 nM), large conductance $Ca^{2+}-activated$ $K^+$ channel blockers, but not by apamin (300 nM), a small conductance $Ca^{2+}-activated$ $K^+$ channel blocker, and glibenclamide ( 1 ${\mu}M$), an ATP-sensitive $K^+$ channel blocker. In conclusion, it is suggested that the CGRP1 receptor, upon activation by CGRP, are coupled to opening of $Ca^{2+}-activated$ $K^+$ channel and cause to decrease in $[Ca^{2+}]_i$, thereby leading to vasodilation of the rat basilar artery. However, it is not defined that the mechanism underlying vasodilation whether the $K^+$ channel blockers, charybdotoxin and iberiotoxin directly block the CGRP receptors and that CGRP-evoked relaxation is dependent on the cyclic AMP or $K^+$ channel opening or both actions.

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The Significance of Acetylcholine Receptor Autoantibody Test (아세틸콜린 수용체 항체(Acetylcholine receptor autoantibody) 검사의 의의)

  • Yoo, Soh-Yeon;Lim, Soo-Yeon;Pack, Song-Ran;Seo, Mi-Hye;Moon, Hyung-Ho;You, Sun-Hee
    • The Korean Journal of Nuclear Medicine Technology
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    • v.15 no.1
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    • pp.113-116
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    • 2011
  • Purpose: Acetylcholine receptor antibodies cause acetylcholine receptor loss, which is responsible for failure of the neuromuscular junction in the acetylcholine receptor autoantibody. The disease characterized by muscle weakness and fatigue, myasthenia gravis(MG) occurs when the body inappropriately produces antibodies against acetylcholine receptors, and thus inhibits proper acetylcholine signal transmission. And this reason, the measurement of acetylcholine receptor antibodies can be of considerable value in disease diagnosis. Methods: From 2010. August to September, we tested orderd AchRAb 19 samples to get the results. 1. Pipette $5{\mu}{\ell}$ undiluted patient sera and kit control and add 125I AChR $50{\mu}{\ell}$ and incubate at R.T for 2 hours. 2. Pipette $50{\mu}{\ell}$ of anti-human IgG into each tube, and incubate at $2{\sim}8^{\circ}C$ for 2 hours. 3. Pipette $25{\mu}{\ell}$ precipitation enhancer into each tube and add 1mL washing solution into all tubes. 4. Centrifuge each tube for 20minutes at $2{\sim}8^{\circ}C$ at 1500g. 5. Aspirate or decant the supernatant. 6. Pipette 1 mL washing solution into all tubes and resuspend the pellet and repeat centrifugation. 7. Aspirate or decant the supernatant and count all tubes on a gamma counter. Results: Cut off value is 0.2 nmol/L and the results taken below 0.2 nmol/L are negative, the results above that identified as being positive values. We assayed the 19 patients samples and got 7 positive results. Of which, 6 patients were diagnosed as MG.(85.7%). Conclusions: Acetylcholine Receptor autoantibody test is intended for use by persons only for the quantitative determination of it in human serum. Even if measurement of the antibodies is not a routine test, it can be of considerable value in disease diagnosis.

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Characterization of Trigeminal Ganglion Neurons Expressing Transient Receptor Potential Ankyrin 1 (TRPA1) in the Rat (흰쥐의 삼차신경절에서 Transient receptor potential ankyrin 1 (TRPA1)의 발현 특성에 관한 연구)

  • Paik, Sang-Kyoo;Na, Yeon-Kyung;Kim, Yun-Sook
    • Applied Microscopy
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    • v.42 no.1
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    • pp.27-33
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    • 2012
  • Transient receptor potential ankyrin 1 (TRPA1), responding to noxious cold (${\leq}17^{\circ}C$) and pungent compounds, is implicated in nociception, but little is known about the coexpression of TRPA1 and other channels or receptors involved in the nociception in craniofacial regions. To address this issue, we characterized the TRPA1-immunopositive (+) neurons in the rat trigeminal ganglion (TG) and investigated their colocalization with other proteins known to be expressed in nociceptive neurons, such as transient receptor potential vanilloid (TRPV1) and $P2X_3$ receptor, using light microscopic immunofluorescence labeling method with TRPA1 and TRPV1 or $P2X_3$ antisera. The majority of TRPA1+ neurons costained for TRPV1 (TRPV1+/TRPA1+; 58.8%, 328/558) and 41.2% only expressed TRPA1 but not TRPV1. The TRPV1+/TRPA1+ neurons were small and medium sized. In addition, we investigated the colocalization of TRPA1 with $P2X_3$, a nonselective cation channel activated by ATP that may be released in the extracellular space as a result of tissue damage and inflammation. Among all TRPA1+ TG neurons, 26.1% (310/1186) costained for $P2X_3$, whereas 73.9% (876/1186) of TRPA1+ neurons did not coexpress $P2X_3$. $P2X_3$+/TRPA1+ neurons were predominantly small and medium sized. These results suggest that TRPA1+ neurons coexpressing TRPV1 or $P2X_3$ are involved in specific roles in the transmission and processing of orofacial nociceptive information by noxious cold, heat, and inflammation.

The Relationship between the Therapeutic Response to Antipsychotic Drugs and the Dopamine D2, D3, and D4 Receptor Gene Polymorphisms in Korean Schizophrenic Patients (한국인 정신분열병 환자에서 항정신병 약물의 치료 반응과 도파민 D2, D3 및 D4 수용체 유전자 다형성)

  • Kim, Hee-Cheol;Jung, Sung-Won;Kim, Dae-Kwang;Jung, Chul-Ho
    • Korean Journal of Biological Psychiatry
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    • v.14 no.3
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    • pp.167-176
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    • 2007
  • Objectives:A considerable number of pharmacogenetic studies have been performed in recent years to define the association of antipsychotic drug response with dopamine receptor polymorphisms. The purpose of this study was to investigate the relationship between the therapeutic response to antipsychotic drugs and the polymorphisms of the dopamine D2, D3, and D4 receptor genes(DRD2, DRD3 and DRD4, respectively). Methods:We conducted retrospective chart review of 200 consecutively hospitalized patients with the diagnosis of schizophrenia(DSM-IV) who were treated with various antipsychotics(94% atypical antipsychotics) at Bugok National Hospital, Korea. The patients were divided into two groups, responders and non-responders, by responsiveness to antipsychotic drugs according to a four-point scale used in previous studies; responders included moderate to marked responded patients and non-responders included none to minimal responded patients. We analyzed the Ser311Cys polymorphism in the DRD2, the Ser9Gly polymorphism in the DRD3, and the exon III 48 bp repeat polymorphism in the DRD4. Results:Among the total patients of 200, 141(70.5%) were categorized as responders. There were no significant differences in the frequencies of the DRD2, DRD3, and DRD4 alleles and genotypes between responders and non-responders. Conclusion:These results suggest that the Ser311Cys polymorphism in the DRD2, the Ser9Gly polym- orphism in the DRD3, and the exon III 48bp repeat polymorphism in the DRD4 are not associated with the therapeutic response to antipsychotic drugs in Korean schizophrenic patients. A larger prospective study is needed to elucidate the association between antipsychotic response and dopamine receptor gene polymorphism.

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Association between Genetic Polymorphism of Peroxisome Proliferator-Activated Receptor Alpha Leu162Val and Metabolioc Syndrome in Korean (한국인에서 peroxisome proliferator-activated receptor alpha Leu162Val 유전자 다형성과 대사증후군간의 관련성)

  • Shin Soung-Cheal;Song Hye-Soon;Hong Young-Seoub;Kwak Jong-Young;Yoo Byung-Chul;Lee Yong-Hwan
    • Journal of Life Science
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    • v.16 no.2 s.75
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    • pp.199-205
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    • 2006
  • Peroxisome proliferator activated receptor (PPAR)-$\alpha$ of three PPAR subtypes ($-\alpha,\;-\beta/-\gamma,\;-\delta$), which are members of the nuclear hormone receptor superfamily of ligand-activated transcription factors, plays a key role in lipoprotein and glucose homeostasis. A variation in the PPAR-a gene expression has been suggested to influence the development of metabolic syndrome through alterations in lipid concentrations. The aim of our study was to investigate the association between the PPAR-a and metabolic syndrome among South Korean. A total of 542 health screen examinees were enrolled in this study who were examined in Kosin University Gospel Hospital from December, 2004 to July, 2005. The height, weight, waist circumference, and systolic and diastolic blood pressure of the subjects were examined and fasting blood glucose, total cholesterol, HDL cholesterol, LDL cholesterol, triglyceride were measured by-sampling in venous blood. The metabolic syndrome was defined as the presence of three or more of the following : waist circumference men ${\geq}90cm$, women ${\geq}80cm$, blood pressure ${\geq}130/85mmHg$, fasting glucose ${\geq}110mg/dL$, HDL cholesterol men <40 mg/dL, women <50 mg/dL, triglyceride ${\geq}150mg/dL$. The blood pressure, fasting glucose, HDL cholesterol, triglyceride were evaluated by using the criteria of NECP ATP III and waist circumference was assessed by using the criteria of WHO Asia-Western Pacific. And the author compared the frequency of the PPAR-$\alpha$ mutation of L162V ($C{\rightarrow}G$ variant in exon 5) in a sample of 542 subjects with and without the metabolic syndrome by polymerase chain reaction allele-specific oligonucleotide (PCR-ASO) method. One (0.2%) hetero-isotype among high risk of metabolic syndrome was identified. The values of waist circumference, body mass index and low density lipoprotein cholesterol of the mutant were 100 cm, 28.6 $kg/m^2$ and 120 mg/dL, respectively. Although the author failed to see significant association between the presence of the PPAR-$\alpha$ L162V polymorphism and metabolic syndrome, one PPAR-$\alpha$ L162V polymorphism in metabolic syndrome patients was found.

The Extended Site Assessment Procedure Based on Knowledge of Biodegradability to Evaluate the Applicability of Intrinsic Remediation (자연내재복원기술(Intrinsic Remediation)적용을 위한 오염지역 평가과정 개발)

  • ;Robert M. Cowan
    • Journal of Korea Soil Environment Society
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    • v.2 no.3
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    • pp.3-21
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    • 1997
  • The remediation of contamiated sites using currently available remediation technologies requires long term treatment and huge costs, and it is uncertain to achieve the remediation goal to drop contamination level to either back-ground or health-based standards by using such technologies. Intrinsic remediation technology is the remediation technology that relies on the mechanisms of natural attenuation for the containment and elimination of contaminants in subsurface environments. Initial costs for the intrinsic remediation may be higher than conventional treatment technologies because the most comprehensive site assessment for intrinsic remediation is required. Total remediation cost, however may be the lowest among the presently employed technologies. The applicability of intrinsic remediation in the contaminated sites should be theroughly investigated to achieve the remedial goal of the technology. This paper provides the frame of the extended site assessment procedure based on knowledge of biodegradability to evaluate the applicability of intrinsic remediation. This site assessment procedure is composed of 5 steps such as preliminary site screening, assessment of the current knowledge of biodegradability, selecting the appropriate approach, analyzing the contaminant fate and transport and planning the monitoring schedule. In the step 1, followings are to be decided 1) whether to go on the the detailed assessment or not based on the rules of thumb concerning the biodegradability of organic compounds, 2) which protocol document is selected to follow for detailed site assessment according to the site characteristics, contaminants and the relative distance between the contamination and potential receptors. In the step 2, the database for biodegradability are searched and evaluated. In the step 3, the appropriate biodegradability pathways for the contaminated site is selected. In the step 4, the fate and transport of the contaminants at the site are analyzed through modeling. In the step 5, the monitoring schedule is planned according to the result of the modeling. Through this procedure, users may able to have the rational and systematic informations for the application of intrinsic remediation. Also the collected data and informations can be used as the basic to re-select the other remediation technology if it reaches a conclusion not to applicate intrinsic remediation technology at the site from the site assessment procedure.

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Evaluation on Removal Efficiency of Methylene Blue Using Nano-ZnO/Laponite/PVA Photocatalyzed Adsorption Ball (Nano-ZnO/Laponite/PVA 광촉매 흡착볼의 메틸렌블루 제거효율 평가)

  • Oh, Ju Hyun;Ahn, Hosang;Jang, Dae Gyu;Ahn, Chang Hyuk;Lee, Saeromi;Joo, Jin Chul
    • Journal of Korean Society of Environmental Engineers
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    • v.35 no.9
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    • pp.636-642
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    • 2013
  • In order to overcome drawbacks (i.e., filtration and recovery) of conventional powder type photocatalysts, nano-ZnO/Laponite/PVA (ZLP) photocatalyzed adsorption balls were developed by using in situ mixing of nanoscale ZnO as a photocatalyst, and Laponite as both adsorbent and supporting media in deionized water, followed by the poly vinyl alcohol polymerization with boric acid. The optimum mixing ratio of nano-ZnO:Laponite:PVA:deionized water was found to be 3:1:1:16 (by weight), and the mesh and film produced by PVA polymerization with boric acid might inhibit both swelling of Laponite and detachment of nanoscale ZnO from ZLP balls. Drying ZLP balls with microwave (600 watt) was found to produce ZLP balls with stable structure in water, and various sizes (55~500 ${\mu}m$) of pore were found to be distributed based on SEM and TEM results. In the initial period of reaction (i. e., 40 min), adsorption through ionic interaction between methylene blue and Laponite was the main removal mechanism. After the saturation of methylene blue to available adsorption sites for Laponite, the photocatalytic degradation of methylene blue occurred. The effective removal of methylene blue was attributed to adsorption and photocatalytic degradation. Based on the results from this study, synthesized ZLP photocatalyzed adsorption balls were expected to remove recalcitrant organic compounds effectively through both adsorption and photocatalytic degradation, and the risks of environmental receptors caused by detachment of nanoscale photocatalysts can be reduced.

Parkin Interacts with the PDZ Domain of Multi-PDZ Domain Protein MUPP1 (Parkin과 Multi-PDZ Domain Protein (MUPP1) 단백질 간의 PDZ 결합)

  • Jang, Won Hee;Jeong, Young Joo;Choi, Sun Hee;Lee, Won Hee;Kim, Mooseong;Kim, Sang-Jin;Urm, Sang-Hwa;Moon, Il Soo;Seog, Dae-Hyun
    • Journal of Life Science
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    • v.24 no.8
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    • pp.820-826
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    • 2014
  • The localization to specific subcellular sites and the regulation of cell surface receptors and channels are crucial for proper functioning. Postsynaptic density-95/Disks large/Zonula occludens-1 (PDZ)-domain is involved in recognition of and interaction between various proteins, by which the localization and the regulation are mediated. Multi-PDZ domain protein 1 (MUPP1) contains 13 PDZ domains. MUPP1 serves a scaffolding function for structure proteins and signaling proteins, but the mechanism how MUPP1 is stabilized and signalized has not yet been elucidated. We used the yeast two-hybrid system to identify proteins that interact with PDZ domains of MUPP1. We found an interaction between MUPP1 and Parkin. Parkin is an E3 ubiquitin ligase. Loss-of-function mutations of Parkin gene are known to cause an autosomal recessive juvenile parkinsonism. Parkin bound to the $12^{th}$ PDZ domain, but not to other PDZ domains of MUPP1. The C-terminal end of Parkin has a type II PDZ-association motif, which was essential for the interaction with MUPP1 in the yeast two-hybrid assay. When co-expressed in HEK-293T cells, Parkin co-localized with MUPP1. When co-expressed with ubiquitin in HEK-293T cells, MUPP1 has been strongly ubiquitinated by Parkin. These findings collectively suggest that MUPP1 is a novel substrate of Parkin and its function or stability could be modulated by Parkin-mediated ubiquitination.