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Cited by 14Genomics and Chromatin DynamicsMechanisms of cancer metastasisProtein Kinase Regulation and GTPase Signaling

P300 regulates the human RLIP76 promoter activity and gene expression

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Sehrawat, Archana, Yadav, Sushma, Awasthi, Yogesh C., Basu, Alakananda, Warden, Charles, Awasthi, Sanjay·2013·Biochemical Pharmacology
DOI 10.1016/j.bcp.2013.02.012PMC PMC3822774
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Abstract

A 76-kDa Ral-interacting protein (RLIP76) has been implicated in the pathogenesis of cancer and diabetes. It is often over expressed in human malignant cell lines and human tumor samples and has been associated with metastasis and chemoresistance. RLIP76 homozygous knockout mice exhibit increased insulin sensitivity, hypoglycemia, and hypolipidemia, and resist cancer development. Little is known about the mechanism by which the expression of RLIP76 is regulated. In the present study, we functionally characterized the RLIP76 promoter using deletion mapping and mutational analysis to investigate the regulation of RLIP76 transcription. We have identified the promoter regions important for RLIP76 transcription, including a strong cis-activating element in the proximal promoter containing overlapping consensus cMYB and cETS binding sites. Transcription factor cMYB and the coactivator p300 associated with RLIP76 gene promoter as shown by CHIP assay. Knockdown of p300 in HEK293 cells reduced the activity of the promoter fragment containing wild type cMYB/cETS binding site in comparison to that with deleted or mutated cMYB/cETS binding site. Knockdown of p300 also decreased the RLIP76 expression as indicated by immunoblotting, immunocytochemistry and flow cytometry analysis. Thus, we report for the first time that p300 associates with the RLIP76 promoter via an overlapping cMYB and cETS binding site and regulates RLIP76 promoter activity and its expression.

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  1. [1]Singhal SS Awasthi YC Awasthi S Regression of melanoma in a murine model by RLIP76 depletion Cancer Res 2006 66 2354 60 16489041
  2. [2]Singhal SS Roth C Leake K Singhal J Yadav S Awasthi S Regression of prostate cancer xenografts by RLIP76 depletion Biochem Pharmacol 2009 77 1074 83 19073149 PMC2683040
  3. [3]Singhal SS Singhal J Yadav S Sahu M Awasthi YC Awasthi S RLIP76: a target for kidney cancer therapy Cancer Res 2009 69 4244 51 19417134 PMC2921230
  4. [4]Smith SC Oxford G Baras AS Owens C Havaleshko D Brautigan DL Expression of ral GTPases, their effectors, and activators in human bladder cancer Clin Cancer Res 2007 13 3803 13 17606711
  5. [5]Durand J Lampron A Mazzuco TL Chapman A Bourdeau I Characterization of differential gene expression in adrenocortical tumors harboring beta-catenin (CTNNB1) mutations J Clin Endocrinol Metab 2011 96 E1206 11 21565795
  6. [6]Jullien-Flores V Dorseuil O Romero F Letourneur F Saragosti S Berger R Bridging Ral GTPase to Rho pathways. RLIP76, a Ral effector with CDC42/Rac GTPase-activating protein activity The Journal of biological chemistry 1995 270 22473 7 7673236
  7. [7]Cantor SB Urano T Feig LA Identification and characterization of Ral-binding protein 1, a potential downstream target of Ral GTPases Mol Cell Biol 1995 15 4578 84 7623849 PMC230698
  8. [8]Park SH Weinberg RA A putative effector of Ral has homology to Rho/Rac GTPase activating proteins Oncogene 1995 11 2349 55 8570186
  9. [9]Awasthi S Cheng J Singhal SS Saini MK Pandya U Pikula S Novel function of human RLIP76: ATP-dependent transport of glutathione conjugates and doxorubicin Biochemistry 2000 39 9327 34 10924126
  10. [10]Awasthi S Cheng JZ Singhal SS Pandya U Sharma R Singh SV Functional reassembly of ATP-dependent xenobiotic transport by the N- and C-terminal domains of RLIP76 and identification of ATP binding sequences Biochemistry 2001 40 4159 68 11300797
  11. [11]Singhal SS Singhal J Sharma R Singh SV Zimniak P Awasthi YC Role of RLIP76 in lung cancer doxorubicin resistance: I. The ATPase activity of RLIP76 correlates with doxorubicin and 4-hydroxynonenal resistance in lung cancer cells International journal of oncology 2003 22 365 75 12527936
  12. [12]Sharma R Singhal SS Wickramarachchi D Awasthi YC Awasthi S RLIP76 (RALBP1)-mediated transport of leukotriene C4 (LTC4) in cancer cells: implications in drug resistance Int J Cancer 2004 112 934 42 15386349
  13. [13]Stuckler D Singhal J Singhal SS Yadav S Awasthi YC Awasthi S RLIP76 transports vinorelbine and mediates drug resistance in non-small cell lung cancer Cancer Res 2005 65 991 8 15705900
  14. [14]Leake K Singhal J Nagaprashantha LD Awasthi S Singhal SS RLIP76 regulates PI3K/Akt signaling and chemo-radiotherapy resistance in pancreatic cancer PLoS One 2012 7 e34582 22509328 PMC3317991
  15. [15]Singhal SS Singhal J Yadav S Dwivedi S Boor PJ Awasthi YC Regression of lung and colon cancer xenografts by depleting or inhibiting RLIP76 (Ral-binding protein 1) Cancer Res 2007 67 4382 9 17483352
  16. [16]Singhal SS Wickramarachchi D Yadav S Singhal J Leake K Vatsyayan R Glutathione-conjugate transport by RLIP76 is required for clathrin-dependent endocytosis and chemical carcinogenesis Mol Cancer Ther 2011 10 16 28 21220488 PMC3065778
  17. [17]Awasthi S Singhal SS Yadav S Singhal J Vatsyayan R Zajac E A central role of RLIP76 in regulation of glycemic control Diabetes 2010 59 714 25 20007934 PMC2828645
  18. [18]Singhal J Nagaprashantha L Vatsyayan R Awasthi S Singhal SS RLIP76, a glutathione-conjugate transporter, plays a major role in the pathogenesis of metabolic syndrome PLoS One 2011 6 e24688 21931813 PMC3172288
  19. [19]Goldfinger LE Ptak C Jeffery ED Shabanowitz J Hunt DF Ginsberg MH RLIP76 (RalBP1) is an R-Ras effector that mediates adhesion-dependent Rac activation and cell migration J Cell Biol 2006 174 877 88 16966426 PMC2064341
  20. [20]Lee S Wurtzel JG Singhal SS Awasthi S Goldfinger LE RALBP1/RLIP76 depletion in mice suppresses tumor growth by inhibiting tumor neovascularization Cancer Res 2012 PMC3473090 22902412
  21. [21]Mollberg NM Steinert G Aigner M Hamm A Lin FJ Elbers H Overexpression of RalBP1 in colorectal cancer is an independent predictor of poor survival and early tumor relapse Cancer Biol Ther 2012 13 694 700 22549157 PMC3408974
  22. [22]Singhal SS Singhal J Nair MP Lacko AG Awasthi YC Awasthi S Doxorubicin transport by RALBP1 and ABCG2 in lung and breast cancer International journal of oncology 2007 30 717 25 17273774
  23. [23]Singhal SS Yadav S Drake K Singhal J Awasthi S Hsf-1 and POB1 induce drug sensitivity and apoptosis by inhibiting Ralbp1 The Journal of biological chemistry 2008 283 19714 29 18474607 PMC2443664
  24. [24]Singhal SS Yadav S Singhal J Zajac E Awasthi YC Awasthi S Depletion of RLIP76 sensitizes lung cancer cells to doxorubicin Biochem Pharmacol 2005 70 481 8 15950949
  25. [25]Singhal SS Yadav S Singhal J Sahu M Sehrawat A Awasthi S Diminished drug transport and augmented radiation sensitivity caused by loss of RLIP76 FEBS Lett 2008 582 3408 14 18789326 PMC2586942
  26. [26]Cheng JZ Sharma R Yang Y Singhal SS Sharma A Saini MK Accelerated metabolism and exclusion of 4-hydroxynonenal through induction of RLIP76 and hGST5. 8 is an early adaptive response of cells to heat and oxidative stress The Journal of biological chemistry 2001 276 41213 23 11522795
  27. [27]Bradford MM A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding Anal Biochem 1976 72 248 54 942051
  28. [28]Lee S Das HK Inhibition of basal activity of c-jun-NH2-terminal kinase (JNK) represses the expression of presenilin-1 by a p53-dependent mechanism Brain Res 2008 1207 19 31 18374905
  29. [29]Singhal J Yadav S Nagaprashantha LD Vatsyayan R Singhal SS Awasthi S Targeting p53-null neuroblastomas through RLIP76 Cancer Prev Res (Phila) 2011 4 879 89 21411502 PMC3107925
  30. [32]Messeguer X Escudero R Farre D Nunez O Martinez J Alba MM PROMO: detection of known transcription regulatory elements using species-tailored searches Bioinformatics 2002 18 333 4 11847087
  31. [33]Farre D Roset R Huerta M Adsuara JE Rosello L Alba MM Identification of patterns in biological sequences at the ALGGEN server: PROMO and MALGEN Nucleic Acids Res 2003 31 3651 3 12824386 PMC169011
  32. [34]Chan HM La Thangue NB p300/CBP proteins: HATs for transcriptional bridges and scaffolds J Cell Sci 2001 114 2363 73 11559745
  33. [35]Jayaraman G Srinivas R Duggan C Ferreira E Swaminathan S Somasundaram K p300/cAMP-responsive element-binding protein interactions with ets-1 and ets-2 in the transcriptional activation of the human stromelysin promoter The Journal of biological chemistry 1999 274 17342 52 10358095
  34. [36]Geng CD Vedeckis WV c-Myb and members of the c-Ets family of transcription factors act as molecular switches to mediate opposite steroid regulation of the human glucocorticoid receptor 1A promoter The Journal of biological chemistry 2005 280 43264 71 16263717
  35. [37]Geng CD Vedeckis WV Steroid-responsive sequences in the human glucocorticoid receptor gene 1A promoter Mol Endocrinol 2004 18 912 24 15044598
  36. [38]Geng CD Schwartz JR Vedeckis WV A conserved molecular mechanism is responsible for the auto-up-regulation of glucocorticoid receptor gene promoters Mol Endocrinol 2008 22 2624 42 18945813 PMC2626199
  37. [39]Shackleford TJ Zhang Q Tian L Vu TT Korapati AL Baumgartner AM Stat3 and CCAAT/enhancer binding protein beta (C/EBP-beta) regulate Jab1/CSN5 expression in mammary carcinoma cells Breast Cancer Res 2011 13 R65 21689417 PMC3218954
  38. [40]Meadows SM Myers CT Krieg PA Regulation of endothelial cell development by ETS transcription factors Semin Cell Dev Biol 2011 22 976 84 21945894 PMC3263765
  39. [41]Bricambert J Miranda J Benhamed F Girard J Postic C Dentin R Salt-inducible kinase 2 links transcriptional coactivator p300 phosphorylation to the prevention of ChREBP-dependent hepatic steatosis in mice J Clin Invest 2010 120 4316 31 21084751 PMC2993582
  40. [42]Chen S Feng B George B Chakrabarti R Chen M Chakrabarti S Transcriptional coactivator p300 regulates glucose-induced gene expression in endothelial cells Am J Physiol Endocrinol Metab 2010 298 E127 37 19903865
  41. [43]Chiu J Khan ZA Farhangkhoee H Chakrabarti S Curcumin prevents diabetes-associated abnormalities in the kidneys by inhibiting p300 and nuclear factor-kappaB Nutrition 2009 25 964 72 19268536
  42. [44]Kaur H Chen S Xin X Chiu J Khan ZA Chakrabarti S Diabetes-induced extracellular matrix protein expression is mediated by transcription coactivator p300 Diabetes 2006 55 3104 11 17065349
  43. [45]Stimson L Rowlands MG Newbatt YM Smith NF Raynaud FI Rogers P Isothiazolones as inhibitors of PCAF and p300 histone acetyltransferase activity Mol Cancer Ther 2005 4 1521 32 16227401
  44. [46]Balasubramanyam K Varier RA Altaf M Swaminathan V Siddappa NB Ranga U Curcumin, a novel p300/CREB-binding protein-specific inhibitor of acetyltransferase, represses the acetylation of histone/nonhistone proteins and histone acetyltransferase-dependent chromatin transcription The Journal of biological chemistry 2004 279 51163 71 15383533
  45. [47]He L Naik K Meng S Cao J Sidhaye AR Ma A Transcriptional Co-activator p300 Maintains Basal Hepatic Gluconeogenesis The Journal of biological chemistry 2012 287 32069 77 22815486 PMC3442537
  46. [48]Awasthi S Singhal SS Singhal J Cheng J Zimniak P Awasthi YC Role of RLIP76 in lung cancer doxorubicin resistance: II. Doxorubicin transport in lung cancer by RLIP76 International journal of oncology 2003 22 713 20 12632060
  47. [49]Awasthi S Singhal SS Awasthi YC Martin B Woo JH Cunningham CC RLIP76 and Cancer Clin Cancer Res 2008 14 4372 7 18628450 PMC2919285
  48. [50]Li M Luo RZ Chen JW Cao Y Lu JB He JH High expression of transcriptional coactivator p300 correlates with aggressive features and poor prognosis of hepatocellular carcinoma J Transl Med 2011 9 5 21205329 PMC3022728
  49. [51]Kung AL Rebel VI Bronson RT Ch’ng LE Sieff CA Livingston DM Gene dose-dependent control of hematopoiesis and hematologic tumor suppression by CBP Genes & development 2000 14 272 7 10673499 PMC316359
  50. [52]Gayther SA Batley SJ Linger L Bannister A Thorpe K Chin SF Mutations truncating the EP300 acetylase in human cancers Nature genetics 2000 24 300 3 10700188
  51. [53]Goodman RH Smolik S CBP/p300 in cell growth, transformation, and development Genes & development 2000 14 1553 77 10887150
  52. [54]Coffer P de Jonge M Mettouchi A Binetruy B Ghysdael J Kruijer W junB promoter regulation: Ras mediated transactivation by c-Ets-1 and c-Ets-2 Oncogene 1994 9 911 21 8108135
  53. [55]Persson M Andren Y Mark J Horlings HM Persson F Stenman G Recurrent fusion of MYB and NFIB transcription factor genes in carcinomas of the breast and head and neck Proceedings of the National Academy of Sciences of the United States of America 2009 106 18740 4 19841262 PMC2773970
  54. [56]Biroccio A Benassi B D’Agnano I D’Angelo C Buglioni S Mottolese M c-Myb and Bcl-x overexpression predicts poor prognosis in colorectal cancer: clinical and experimental findings The American journal of pathology 2001 158 1289 99 11290547 PMC1891926
  55. [57]De la Houssaye G Vieira V Masson C Beermann F Dufier JL Menasche M ETS-1 and ETS-2 are upregulated in a transgenic mouse model of pigmented ocular neoplasm Molecular vision 2008 14 1912 28 18958307 PMC2573735
  56. [58]Rostad K Mannelqvist M Halvorsen OJ Oyan AM Bo TH Stordrange L ERG upregulation and related ETS transcription factors in prostate cancer International journal of oncology 2007 30 19 32 17143509

Cited by

Sorted by citations

Authors
Sehrawat, A., Yadav, S., Awasthi, Y. C., Basu, A., Warden, C., & Awasthi, S.
Affiliations
  • University of North Texas Health Science Center (US)
  • City Of Hope National Medical Center (US)
ORCID
Venue
Biochemical Pharmacology
Publisher
Elsevier BV
Published
2013-04
Volume
85
Issue
8
Pages
1203-1211
ISSN
0006-2952 (ISSN-L)
DOI
10.1016/j.bcp.2013.02.012
PMC
PMC3822774
OpenAlex
W2092143393
Cited by
14
References
0
Citations by year
2024: 1 · 2022: 4 · 2021: 1 · 2018: 2 · 2017: 2 · 2016: 1 · 2014: 1 · 2013: 2
FWCI
0.60
Type
journal article
Language
en
Open access
Locations
  • Biochemical Pharmacology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • University of North Texas
  • National Institutes of Health
  • National Cancer Institute (CA 77495, R01CA077495)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Keywords
RLIP76, P300, promoter regulation, transcriptional regulation, crosstalk, MYB, transcriptional coactivator, gene expression
MeSH terms
Base Sequence, Binding Sites, Gene Expression Regulation, Humans, Molecular Sequence Data, Neoplasms, Promoter Regions, Genetic, RNA, Messenger, ATP-Binding Cassette Transporters, Proto-Oncogene Proteins c-myb, GTPase-Activating Proteins, Proto-Oncogene Proteins c-ets, E1A-Associated p300 Protein, HEK293 Cells

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