Research Topics
Genomes and Genes
| Sunil C KaulSummaryAffiliation: National Institute of Advanced Industrial Science and Technology Country: Japan Publications
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Detail Information
Publications
Overexpressed mortalin (mot-2)/mthsp70/GRP75 and hTERT cooperate to extend the in vitro lifespan of human fibroblastsSunil C Kaul
National Institute of Advanced Industrial Science and Technology AIST, 1 1 1 Higashi, Tsukuba, Ibaraki 305 8566, Japan
Exp Cell Res 286:96-101. 2003..Together, mot-2 and hTERT permitted bypass of senescence, a substantial extension of lifespan, and possibly immortalization. This is the first demonstration that mot-2 and telomerase can cooperate in the immortalization process...
CARF regulates p19ARF-p53-p21WAF1 senescence pathway by multiple checkpointsSunil C Kaul
National Institute of Advanced Industrial Science and Technology AIST, Tsukuba, Ibaraki, Japan
Ann N Y Acad Sci 1067:217-9. 2006..In the nucleoplasm, CARF interacts with p53 and enhances its function. We demonstrate that p53 downregulates CARF in a negative feedback regulatory loop and may also involve p53 antagonist HDM2...
Proproliferative functions of Drosophila small mitochondrial heat shock protein 22 in human cellsRenu Wadhwa
National Institute of Advanced Industrial Science and Technology, Central 4, 1 1 1 Higashi, Tsukuba, Ibaraki 305 8562, Japan
J Biol Chem 285:3833-9. 2010..We report that the DmHsp22 interacts and inactivates wild type tumor suppressor protein p53, which may be one possible way of its functioning in human cells...
Upregulation of mortalin/mthsp70/Grp75 contributes to human carcinogenesisRenu Wadhwa
Gene Function Research Center, National Institute of Advanced Industrial Science and Technology AIST, Tsukuba, Ibaraki, Japan
Int J Cancer 118:2973-80. 2006..The study demonstrates that upregulation of mortalin contributes significantly to tumorigenesis, and thus is a good candidate target for cancer therapy...
Identification and characterization of molecular interactions between mortalin/mtHsp70 and HSP60Renu Wadhwa
Gene Function Research Center, National Institute of Advanced Industrial Science and Technology AIST, 1 1 1 Higashi, Tsukuba, Ibaraki 305 8562, Japan
Biochem J 391:185-90. 2005....
Glycerol stimulates innate chaperoning, proteasomal and stress-resistance functions: implications for geronto-manipulationCuster C Deocaris
National Institute of Advanced Industrial Science and Technology AIST, Central 4, 1 1 1 Higashi, Tsukuba, 305 8562, Japan
Biogerontology 9:269-82. 2008..These results may have significant implications in the use of glycerol as a candidate geronto-modulator in development of practical interventions for "healthy aging"...
Quantum dot-based protein imaging and functional significance of two mitochondrial chaperones in cellular senescence and carcinogenesisZeenia Kaul
National Institute of Advanced Industrial Science and Technology (AIST, Tsukuba, Ibaraki, Japan
Ann N Y Acad Sci 1067:469-73. 2006..We demonstrate the minute differences in subcellular distribution of mortalin and HSP60, their involvement in tumorigenesis, and functional distinction in pathways involved in senescence...
Stress chaperones, mortalin, and pex19p mediate 5-aza-2' deoxycytidine-induced senescence of cancer cells by DNA methylation-independent pathwayNashi Widodo
National Institute of Advanced Industrial Science and Technology AIST, Central 4, 1 1 1, Higashi, Tsukuba, Ibaraki, Japan
J Gerontol A Biol Sci Med Sci 62:246-55. 2007..We conclude that both mortalin and Pex19p are important mediators, prognostic indicators, and tailoring tools for 5AZA-dC-induced senescence in cancer cells...
CARF (collaborator of ARF) interacts with HDM2: evidence for a novel regulatory feedback regulation of CARF-p53-HDM2-p21WAF1 pathwayM Kamrul Hasan
National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki 305 8562, Japan
Int J Oncol 32:663-71. 2008..By overexpression and silencing studies, we demonstrated that CARF exerts a vital control on the p53-HDM2-p21WAF1 pathway that is frequently altered in cancer cells...
Activation of wild type p53 function by its mortalin-binding, cytoplasmically localizing carboxyl terminus peptidesSunil C Kaul
Gene Function Research Center, National Institute of Advanced Industrial Science and Technology AIST, 1 1 1 Higashi, Tsukuba Science City 305 8562, Japan
J Biol Chem 280:39373-9. 2005..Such activation of p53 function was sufficient to cause growth arrest of human osteosarcoma and breast carcinoma cells...
Deceleration of senescence in normal human fibroblasts by withanone extracted from ashwagandha leavesNashi Widodo
National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki, Japan
J Gerontol A Biol Sci Med Sci 64:1031-8. 2009..To the best of our knowledge, we provide the first example of phytochemical(s) (i-Extract and withanone) that have both anticancer and antiaging activities and point to the molecular link between aging and cancer...
Functional significance of minor structural and expression changes in stress chaperone mortalinCuster C Deocaris
Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan
Ann N Y Acad Sci 1119:165-75. 2007..Besides being validated as a reliable target for cancer therapy, mortalin also warrants attention from the perspectives of management of old-age diseases and healthy aging...
Ashwagandha leaf derived withanone protects normal human cells against the toxicity of methoxyacetic acid, a major industrial metaboliteDidik Priyandoko
National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki, Japan
PLoS ONE 6:e19552. 2011..These findings warrant further basic and clinical studies that may promote the use of withanone as a health adjuvant in a variety of consumer products where the toxicity has been a concern because of the use of ester phthalates...
Alternative reading frame protein (ARF)-independent function of CARF (collaborator of ARF) involves its interactions with p53: evidence for a novel p53-activation pathway and its negative feedback controlMd Kamrul Hasan
Gene Function Research Center, National Institute of Advanced Industrial Science and Technology AIST, 1 1 1 Higashi, Tsukuba, Ibaraki 305 8562, Japan
Biochem J 380:605-10. 2004....
Selective killing of cancer cells by leaf extract of Ashwagandha: components, activity and pathway analysesNashi Widodo
National Institute of Advanced Industrial Science and Technology AIST, Central, Higashi, Tsukuba, Ibaraki, Japan
Cancer Lett 262:37-47. 2008....
CARF: an emerging regulator of p53 tumor suppressor and senescence pathwayCaroline T Y Cheung
National Institute of Advanced Industrial Science and Technology, Central 4, 1 1 1 Higashi, Tsukuba, Ibaraki 305 8562, Japan
Mech Ageing Dev 130:18-23. 2009..The aim of this article is to discuss the current knowledge about functions of CARF and its impact on p53 pathway in regulation of senescence and carcinogenesis...
CARF Is a vital dual regulator of cellular senescence and apoptosisKamrul Hasan
National Institute of Advanced Industrial Science and Technology AIST, 1 1 1 Higashi, Tsukuba, Ibaraki 305 8562, Japan
J Biol Chem 284:1664-72. 2009..We provide evidence that CARF plays a dual role in regulating p53-mediated senescence and apoptosis, the two major tumor suppressor mechanisms...
CARF is a novel protein that cooperates with mouse p19ARF (human p14ARF) in activating p53Md Kamrul Hasan
Research Center for Glycoscience, National Institute of Advanced Industrial Science and Technology AIST, 1 1 1 Higashi, Tsukuba, Ibaraki 305 8566, Japan
J Biol Chem 277:37765-70. 2002..It co-localizes and interacts with ARF in the nucleolus. We demonstrate that CARF is co-regulated with ARF, cooperates with it in activating p53, and thus acts as a novel component of the ARF-p53-p21 pathway...
Effect of the alcoholic extract of Ashwagandha leaves and its components on proliferation, migration, and differentiation of glioblastoma cells: combinational approach for enhanced differentiationNavjot Shah
National Institute of Advanced Industrial Science and Technology, University if Tsukuba, Ibaraki, Japan
Cancer Sci 100:1740-7. 2009..These assays led us to formulate a unique combination formula of i-Extract components that caused enhanced differentiation of glial cells...
Reduction in mortalin level by its antisense expression causes senescence-like growth arrest in human immortalized cellsRenu Wadhwa
National Institute of Advanced Industrial Science and Technology, 1-1-1 Higashi, Tsukuba, Ibaraki 305- 8562, Japan
J Gene Med 6:439-44. 2004..CONCLUSIONS: The data demonstrate that suppression of mortalin is sufficient to induce growth arrest in human immortalized cells that have compromised p53 and pRB functions and possess telomerase activity...
Fate of bone marrow mesenchymal stem cells following the allogeneic transplantation of cartilaginous aggregates into osteochondral defects of rabbitsTomokazu Yoshioka
Department of Orthopaedic Surgery, University of Tsukuba, Ibaraki, Japan
J Tissue Eng Regen Med 5:437-43. 2011..The results suggest that i-MSCs did not inhibit, and indeed contributed to, the regeneration of osteochondral defects...
Mortalin-MPD (mevalonate pyrophosphate decarboxylase) interactions and their role in control of cellular proliferationRenu Wadhwa
National Institute of Advanced Industrial Science and Technology, 1 1 1 Higashi, Tsukuba, Ibaraki 305 8566, Japan
Biochem Biophys Res Commun 302:735-42. 2003..Ras and its oncogenic forms act as key players in controlling proliferation of normal and cancerous cells. Assigning mot-2 upstream of p21(Ras) offers an important mechanism for influence over cell proliferation...
Quantum dot-based mortalin staining as a visual assay for detection of induced senescence in cancer cellsZeenia Kaul
Research Institute for Cell Engineering, National Institute of Advanced Industrial Science and Technology AIST, Central 4, 1 1 1 Higashi, Tsukuba, Ibaraki 305 8562, Japan
Ann N Y Acad Sci 1100:368-72. 2007..Based on the superior resolution, stability and inertness, we propose the use of QD staining of mortalin as a cell-based visual assay to screen for senescence-inducing drugs, proteins, and siRNAs...
Targeting mortalin using conventional and RNA-helicase-coupled hammerhead ribozymesRenu Wadhwa
Gene Function Research Center, National Institute of Advanced Industrial Science and Technology, 1-1-1 Higashi, Tsukuba, Ibaraki, 305-8566, Japan
EMBO Rep 4:595-601. 2003....
CARF binds to three members (ARF, p53, and HDM2) of the p53 tumor-suppressor pathwayHasan M Kamrul
Research Institute for Cell Engineering, National Institute of Advanced Industrial Science and Technology AIST, Central 4, 1 1 1 Higashi, Tsukuba, Ibaraki 305 8562, Japan
Ann N Y Acad Sci 1100:312-5. 2007..CARF may exert a vital control on p53-HDM2-p21(WAF1) pathway that is central to the cell cycle control, senescence, and DNA damage response of human cells...
Involvement of mortalin in cellular senescence from the perspective of its mitochondrial import, chaperone, and oxidative stress management functionsTomoko Yaguchi
Research Institute for Cell Engineering, National Institute of Advanced Industrial Science and Technology AIST, Central 4, 1 1 1 Higashi, Tsukuba, Ibaraki 305 8562, Japan
Ann N Y Acad Sci 1100:306-11. 2007....
A novel putative collaborator of p19ARFRenu Wadhwa
Gene Function Research Laboratory, National Institute of Advanced Industrial Science and Technology, 1 1 1 Higashi, Tsukuba, Ibaraki 305 8566, Japan
Exp Gerontol 38:245-52. 2003..CARF is a novel binding partner of ARF and might be involved in its p53-dependent or -independent tumor suppressive functions...
Selective killing of cancer cells by leaf extract of Ashwagandha: identification of a tumor-inhibitory factor and the first molecular insights to its effectNashi Widodo
Research Institute for Cell Engineering, GENE Therapeutics, Inc, National Institute of Advanced Industrial Science and Technology, Higashi, Tsukuba, Japan
Clin Cancer Res 13:2298-306. 2007..We undertook a study to identify and characterize the antitumor activity of the leaf extract of ashwagandha...
Mortalin imaging in normal and cancer cells with quantum dot immuno-conjugatesZeenia Kaul
National Institute of Advanced Industrial Science and Technology AIST, 1 1 1 Higashi, Tsukuba, Ibaraki 3058562, Japan
Cell Res 13:503-7. 2003..Mortalin staining pattern with quantum dots in both normal and cancer cells mimicked those obtained with organic florescence probes and were considerably stable...
Merger of ayurveda and tissue culture-based functional genomics: inspirations from systems biologyCuster C Deocaris
National Institute of Advanced Industrial Science and Technology AIST, Central 4, 1 1 1 Higashi, Tsukuba, Ibaraki 305 8562, Japan
J Transl Med 6:14. 2008....
Mortalin sensitizes human cancer cells to MKT-077-induced senescenceCuster C Deocaris
National Institute of Advanced Industrial Science and Technology AIST, Central 4, 1 1 1 Higashi, Tsukuba, Ibaraki 305 8562, Japan
Cancer Lett 252:259-69. 2007..Our work may likely translate to a re-appraisal of the therapeutic benefits of low doses of several classes of anti-tumor drugs, even of those that had been discontinued due to adverse effects...
Internalizing antibody-based targeted gene delivery for human cancer cellsMaki Shiota
National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki 305 8562, Japan
Hum Gene Ther 18:1153-60. 2007....
Selective killing of cancer cells by Ashwagandha leaf extract and its component Withanone involves ROS signalingNashi Widodo
National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki, Japan
PLoS ONE 5:e13536. 2010..In the present study, we investigated its mechanism by loss-of-function screening (abrogation of i-Extract induced cancer cell killing) of the cellular targets and gene pathways...
Geroprotection by glycerol: insights to its mechanisms and clinical potentialsCuster C Deocaris
National Institute of Advanced Industrial Science and Technology (AIST, Tsukuba, Japan
Ann N Y Acad Sci 1067:488-92. 2006..This was accompanied by decrease in p53, an upregulation of a stress chaperone mortalin/mtHsp70, and an increase in proteasome activity in the presence of oxidative stress...
From proliferative to neurological role of an hsp70 stress chaperone, mortalinCuster C Deocaris
Institute of Health and Sports Science, University of Tsukuba, Ibaraki, 305 8574, Japan
Biogerontology 9:391-403. 2008..Inversely, it may also seem that vulnerability to mitochondrial dysfunction could be precipitated by malevolent (anti-chaperone) gain-of-function of a 'sick mortalin'...
Use of a randomized hybrid ribozyme library for identification of genes involved in muscle differentiationRenu Wadhwa
Gene Function Research Center, National Institute of Advanced Industrial Science and Technology, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8562, Japan
J Biol Chem 279:51622-9. 2004..This functional gene screening is not only helpful in understanding the molecular pathways of muscle differentiation but also to design molecular strategies for myopathologic therapies...
Molecular bridging of aging and cancer: A CARF linkCaroline T Cheung
National Institute of Advanced Industrial Science and Technology, Ibaraki, Japan
Ann N Y Acad Sci 1197:129-33. 2010..Most recently, we have found that CARF causes bidirectional regulation of p53 and pRB pathways, either arresting or promoting growth, and thus, it could be a potential threshold link between aging and cancer...
MicroRNA-296 is enriched in cancer cells and downregulates p21WAF1 mRNA expression via interaction with its 3' untranslated regionA Rum Yoon
National Institute of Advanced Industrial Science and Technology, Central 4, 1 1 1 Higashi, Tsukuba, Ibaraki 305 8562, Japan
Nucleic Acids Res 39:8078-91. 2011..We demonstrate for the first time that miR-296 is frequently upregulated during immortalization of human cells and contributes to carcinogenesis by downregulation of p53-p21(WAF1) pathway...
Ski is involved in transcriptional regulation by the repressor and full-length forms of Gli3Ping Dai
Laboratory of Molecular Genetics, RIKEN Tsukuba Institute, Ibaraki, Japan
Genes Dev 16:2843-8. 2002..Furthermore, a Ski mutation enhanced the digit abnormalities caused by the Gli3 gene mutation. Thus, Ski plays an important role in pattern formation...
Three faces of mortalin: a housekeeper, guardian and killerSunil C Kaul
National Institute of Advanced Industrial Science and Technology, Tsukuba, Central 4, 1 1 1 Higashi, Tsukuba, Ibaraki 305 8562, Japan
Exp Gerontol 42:263-74. 2007..Being proved to be an attractive target for cancer therapy, it also warrants attention from the perspectives of management of old age diseases and healthy aging...
Structural and functional differences between mouse mot-1 and mot-2 proteins that differ in two amino acidsCuster C Deocaris
National Institute of Advanced Industrial Science and Technology (AIST, Tsukuba, Japan
Ann N Y Acad Sci 1067:220-3. 2006..Here, we provide evidence that mot-1 possesses very low chaperone activity as compared to mot-2. A "lazy lid" hypothesis is proposed for their differential aging phenotypes...
A major functional difference between the mouse and human ARF tumor suppressor proteinsRenu Wadhwa
Gene Function Research Laboratory, Research Center for Glycoscience, National Institute of Advanced Industrial Science and Technology AIST, 1 1 1 Higashi, Tsukuba, Ibaraki 305 8566, Japan
J Biol Chem 277:36665-70. 2002..In view of the major role of ARF in tumor suppression, this distinction may contribute to the different levels of tumor proneness of these species...
Hsp70 family member, mot-2/mthsp70/GRP75, binds to the cytoplasmic sequestration domain of the p53 proteinRenu Wadhwa
Chugai Research Institute for Medical Sciences, 153 2 Nagai, Niihari Mura, Ibaraki, 300 41, Japan
Exp Cell Res 274:246-53. 2002..Therefore, perturbation of mot-p53 interactions can be employed to abrogate cytoplasmic retention of wild-type p53 in tumors...
Mortalin: present and prospectiveSunil C Kaul
Research Center for Glycoscience, National Institute of Advanced Industrial Science and Technology AIST, 1 1 1 Higashi, Tsukuba, Ibaraki 305 8566, Japan
Exp Gerontol 37:1157-64. 2002..Depending on its different subcellular niche and binding partner therein, mortalin is expected to perform multiple functions relevant to cell survival, control of proliferation and stress response...
Quantum dots in bio-imaging: Revolution by the smallHarinder Arya
Gene Function Research Center, National Institute of Advanced Industrial Science and Technology (AIST, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8562, Japan
Biochem Biophys Res Commun 329:1173-7. 2005..Within a decade, research on QDs has evolved from being a pure science subject to the one with high-end commercial applications...
Stable and nondisruptive in vitro/in vivo labeling of mesenchymal stem cells by internalizing quantum dotsYoshimi Ohyabu
National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki, Japan
Hum Gene Ther 20:217-24. 2009..The i-QD-labeled MSCs underwent normal adipocyte, osteocyte, and chondrocyte differentiation in vitro and in vivo, suggesting the potential application of i-QDs in in vivo diagnostics, regenerative and therapeutic medicine...
The versatile stress protein mortalin as a chaperone therapeutic agentCuster C Deocaris
Institute of Health and Sports Sciences, University of Tsukuba, 1 1 1 Tennoudai, Tsukuba, Japan
Protein Pept Lett 16:517-29. 2009..could be creatively applied in a clinical setting to manage stress and to treat various chaperone-based maladies or "chaperonopathies"...
Vectors for RNA interferenceRenu Wadhwa
National Institute of Advanced Industrial Science and Technology, Gene Function Research Center, 1 1 1 Higashi, Tsukuba, Ibaraki 305 8562, Japan
Curr Opin Mol Ther 6:367-72. 2004..This review describes the basis for, and methodology of siRNA expression vectors for mammalian cells...
Druggability of mortalin for cancer and neuro-degenerative disordersCuster C Deocaris
National Institute of Advanced Industrial Science and Technology, Central 4, 1 1 1 Higashi, Tsukuba, Ibaraki 305 8562, Japan
Curr Pharm Des 19:418-29. 2013..As we demystify its deux de machina, accumulating evidence reveal that mortalin may be "druggable" bidirectionally to either treat cancer or neuro-degenerative disorders...
Identification of metastasis-related genes in a mouse model using a library of randomized ribozymesEigo Suyama
Department of Chemistry and Biotechnology, School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan
J Biol Chem 279:38083-6. 2004..The further characterization of these candidate genes would provide clues to the complex mechanism(s) of metastasis...
Rhodacyanine dye MKT-077 inhibits in vitro telomerase assay but has no detectable effects on telomerase activity in vivoRenu Wadhwa
Gene Discovery Research Center, National Institute of Advanced Industrial Science and Technology, Ibaraki 305-8566, Japan
Cancer Res 62:4434-8. 2002..The data suggested that inhibition of telomerase activity is unlikely to be a prime cause of MKT-077-induced toxicity in cancer cells...
LIM kinase-2 targeting as a possible anti-metastasis therapyEigo Suyama
Department of Chemistry and Biotechnology, School of Engineering, The University of Tokyo, Hongo, Tokyo 113-8656, Japan
J Gene Med 6:357-63. 2004..CONCLUSIONS: Specific targeting of metastatic and malignant properties of tumor cells by LIMK-2 ribozyme may serve as an effective therapy for invasive tumors with minimum effect on the surrounding normal cells...
Dose and dose-rate effects of low-dose ionizing radiation on activation of Trp53 in immortalized murine cellsTakashi Sugihara
Department of Radiobiology, Institute for Environmental Sciences, 1 7 Ienomae, Obuchi, Rokkasho, Kamikita, Aomori 039 3212, Japan
Radiat Res 162:296-307. 2004..These results show that cellular response to radiation depended on the dose rate used; i.e., the responses seen at dose rates from 0.1-1 cGy/h were different from those observed at dose rates over 5 cGy/h...
Know-how of RNA interference and its applications in research and therapyRenu Wadhwa
Gene Function Research Center, National Institute of Advanced Industrial, Science and Technology, 1-1-1 Higashi, Tsukuba 305-8562, Japan
Mutat Res 567:71-84. 2004..There is no doubt that further progress in understanding the mechanism of their action as well as strategies to achieve their tightly regulated and tissue specific expression will revolutionize basic and applied biomedical research...
Imminent approaches towards molecular interventions in ageingRenu Wadhwa
Gene Function Research Center, National Institute of Advanced Industrial Science and Technology (AIST, 1-1-1 Higashi, Tsukuba Science City 305-8562, Japan
Mech Ageing Dev 126:481-90. 2005..These post-genomic technologies will help us in the discovery of gene targets for interventions aiming to improve the quality at later years of life beyond their mere algebraic extension...
Use of ribozymes in cellular aging researchCuster C Deocaris
National Institute of Advanced Indutrial Science and Technology AIST, Tsukuba Scince City, Japan
Methods Mol Biol 371:209-26. 2007....
