Glutaminase 2 is a novel negative regulator of small GTPase Rac1 and mediates p53 function in suppressing metastasis

eLife

Volumn 5, Issue JANUARY2016, 2016, Pages

  Zhang, Cen ^a   Liu, Juan ^a   Zhao, Yuhan ^a   Yue, Xuetian ^a   Zhu, Yu ^a,b   Wang, Xiaolong ^a   Wu, Hao ^a   Blanco, Felix ^a   Li, Shaohua ^c   Bhanot, Gyan ^d   Haffty, Bruce G ^a   Hu, Wenwei ^a   Feng, Zhaohui ^a  

^a RUTGERS CANCER INSTITUTE OF NEW JERSEY   (United States)

^b ZHEJIANG UNIVERSITY SCHOOL OF MEDICINE   (China)

^c ROBERT WOOD JOHNSON MEDICAL SCHOOL   (United States)

^d RUTGERS UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BINDING PROTEIN; GLUTAMINASE; GUANINE NUCLEOTIDE EXCHANGE FACTOR; GUANOSINE TRIPHOSPHATE; PROTEIN P53; GLS2 PROTEIN, HUMAN; PROTEIN BINDING; RAC1 PROTEIN;

ARTICLE; CARCINOGENESIS; CELL INVASION ASSAY; CELL MIGRATION ASSAY; CELL VIABILITY; GENE DELETION; HUMAN; IMMUNOBLOTTING; IMMUNOPRECIPITATION; LIQUID CHROMATOGRAPHY; LIVER CELL CARCINOMA; LUNG METASTASIS; METASTASIS; PHOSPHORYLATION; PROTEIN EXPRESSION; PROTEIN INTERACTION; REAL TIME POLYMERASE CHAIN REACTION; TANDEM MASS SPECTROMETRY; WESTERN BLOTTING; METABOLISM; TUMOR CELL LINE;

CELL LINE, TUMOR; GLUTAMINASE; HUMANS; NEOPLASM METASTASIS; PROTEIN BINDING; RAC1 GTP-BINDING PROTEIN; TUMOR SUPPRESSOR PROTEIN P53;

EID: 84963574872     PISSN: None     EISSN: 2050084X     Source Type: Journal    
DOI: 10.7554/eLife.10727     Document Type: Article

References (47)

1. Berkers CR, Maddocks ODK, Cheung EC, Mor I, Vousden KH. 2013. Metabolic regulation by p53 family members. Cell Metabolism 18:617-633. doi: 10.1016/j.cmet.2013.06.019
2. Bid HK, Roberts RD, Manchanda PK, Houghton PJ. 2013. RAC1: an emerging therapeutic option for targeting cancer angiogenesis and metastasis. Molecular Cancer Therapeutics 12:1925-1934. doi: 10.1158/1535-7163.MCT-13-0164
3. Boisguerin P, Leben R, Ay B, Radziwill G, Moelling K, Dong L, Volkmer-Engert R. 2004. An improved method for the synthesis of cellulose membrane-bound peptides with free c termini is useful for PDZ domain binding studies. Chemistry & Biology 11:449-459. doi: 10.1016/j.chembiol.2004.03.010
4. Bosco EE, Ni W, Wang L, Guo F, Johnson JF, Zheng Y. 2010. Rac1 targeting suppresses p53 deficiency-mediated lymphomagenesis. Blood 115:3320-3328. doi: 10.1182/blood-2009-02-202440
5. Cairns RA, Harris IS, Mak TW. 2011. Regulation of cancer cell metabolism. Nature Reviews Cancer 11:85-95. doi:10.1038/nrc2981
6. Castillo-Lluva S, Tatham MH, Jones RC, Jaffray EG, Edmondson RD, Hay RT, Malliri A. 2010. SUMOylation of the GTPase Rac1 is required for optimal cell migration. Nature Cell Biology 12:1078-1085. doi: 10.1038/ncb2112
7. Cherfils J, Zeghouf M. 2013. Regulation of small GTPases by GEFs, GAPs, and GDIs. Physiological Reviews 93:269-309. doi: 10.1152/physrev.00003.2012
8. Chong C, Tan L, Lim L, Manser E. 2001. The mechanism of PAK activation: Autophosphorylation events in both regulatory and kinase domains control activity. Journal of Biological Chemistry 276:17347-17353. doi: 10.1074/jbc.M009316200
9. DeBerardinis RJ, Mancuso A, Daikhin E, Nissim I, Yudkoff M, Wehrli S, Thompson CB. 2007. Beyond aerobic glycolysis: transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis. Proceedings of the National Academy of Sciences 104:19345-19350. doi: 10.1073/pnas.0709747104
10. El-Serag HB, Rudolph KL. 2007. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology 132:2557-2576. doi: 10.1053/j.gastro.2007.04.061
11. Feig LA. 1999. Tools of the trade: use of dominant-inhibitory mutants of ras-family GTPases. Nature Cell Biology 1:E25-E27. doi: 10.1038/10018
12. Fukata M, Watanabe T, Noritake J, Nakagawa M, Yamaga M, Kuroda S, Matsuura Y, Iwamatsu A, Perez F, Kaibuchi K. 2002. Rac1 and Cdc42 capture microtubules through IQGAP1 and CLIP-170. Cell 109:873-885. doi:10.1016/S0092-8674(02)00800-0
13. Galic M, Tsai F-C, Collins SR, Matis M, Bandara S, Meyer T. 2014. Dynamic recruitment of the curvature-sensitive protein ArhGAP44 to nanoscale membrane deformations limits exploratory filopodia initiation in neurons. eLife 3:e03116. doi: 10.7554/eLife.03116
14. Gao P, Tchernyshyov I, Chang T-C, Lee Y-S, Kita K, Ochi T, Zeller KI, De Marzo AM, Van Eyk JE, Mendell JT, Dang CV. 2009. C-myc suppression of miR-23a/b enhances mitochondrial glutaminase expression and glutamine metabolism. Nature 458:762-765. doi: 10.1038/nature07823
15. Guo F, Zheng Y. 2004. Rho family GTPases cooperate with p53 deletion to promote primary mouse embryonic fibroblast cell invasion. Oncogene 23:5577-5585. doi: 10.1038/sj.onc.1207752
16. Hayashi-Takagi A, Takaki M, Graziane N, Seshadri S, Murdoch H, Dunlop AJ, Makino Y, Seshadri AJ, Ishizuka K, Srivastava DP, Xie Z, Baraban JM, Houslay MD, Tomoda T, Brandon NJ, Kamiya A, Yan Z, Penzes P, Sawa A. 2010. Disrupted-in-schizophrenia 1 (dISC1) regulates spines of the glutamate synapse via Rac1. Nature Neuroscience 13:327-332. doi: 10.1038/nn.2487
17. He X, Liu J, Qi Y, Brakebusch C, Chrostek-Grashoff A, Edgar D, Yurchenco PD, Corbett SA, Lowry SF, Graham AM, Han Y, Li S. 2010. Rac1 is essential for basement membrane-dependent epiblast survival. Molecular and Cellular Biology 30:3569-3581. doi: 10.1128/MCB.01366-09
18. Heasman SJ, Ridley AJ. 2008. Mammalian rho GTPases: new insights into their functions from in vivo studies. Nature Reviews Molecular Cell Biology 9:690-701. doi: 10.1038/nrm2476
19. Hensley CT, Wasti AT, DeBerardinis RJ. 2013. Glutamine and cancer: cell biology, physiology, and clinical opportunities. Journal of Clinical Investigation 123:3678-3684. doi: 10.1172/JCI69600
20. Heo J, Thapar R, Campbell SL. 2005. Recognition and activation of rho GTPases by Vav1 and Vav2 guanine nucleotide exchange factors. Biochemistry 44:6573-6585. doi: 10.1021/bi047443q
21. Hu W, Zhang C, Wu R, Sun Y, Levine A, Feng Z. 2010. Glutaminase 2, a novel p53 target gene regulating energy metabolism and antioxidant function. Proceedings of the National Academy of Sciences 107:7455-7460. doi:10.1073/pnas.1001006107
22. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. 2011. Global cancer statistics. CA: A Cancer Journal for Clinicians 61:69-90. doi: 10.3322/caac.20107
23. Kitano K, Murayama T, Sakamoto M, Nagayama K, Ueno K, Murakawa T, Nakajima J. 2012. Outcome and survival analysis of pulmonary metastasectomy for hepatocellular carcinoma. European Journal of Cardio-Thoracic Surgery 41:376-382. doi: 10.1016/j.ejcts.2011.05.052
24. Li X, Yang Q, Yu H, Wu L, Zhao Y, Zhang C, Yue X, Liu Z, Wu H, Haffty BG, Feng Z, Hu W. 2014. LIF promotes tumorigenesis and metastasis of breast cancer through the AKT-mTOR pathway. Oncotarget 5:788-801. doi:10.18632/oncotarget.1772
25. Liu J, Zhang C, Lin M, Zhu W, Liang Y, Hong X, Zhao Y, Young KH, Hu W, Feng Z. 2014a. Glutaminase 2 negatively regulates the PI3K/AKT signaling and shows tumor suppression activity in human hepatocellular carcinoma. Oncotarget 5:2635-2647. doi: 10.18632/oncotarget.1862
26. Liu J, Zhang C, Wang XL, Ly P, Belyi V, Xu-Monette ZY, Young KH, Hu W, Feng Z. 2014. E3 ubiquitin ligase TRIM32 negatively regulates tumor suppressor p53 to promote tumorigenesis. Cell Death and Differentiation 21:1792-1804. doi: 10.1038/cdd.2014.121
27. Muller PAJ, Vousden KH, Norman JC. 2011. P53 and its mutants in tumor cell migration and invasion. The Journal of Cell Biology 192:209-218. doi: 10.1083/jcb.201009059
28. Olalla Lucı-a, Aledo JC, Bannenberg G, Márquez J. 2001. The c-terminus of human glutaminase l mediates association with PDZ domain-containing proteins. FEBS Letters 488:116-122. doi: 10.1016/S0014-5793(00)02373-5
29. Palacios F, Schweitzer JK, Boshans RL, D’Souza-Schorey C. 2002. ARF6-GTP recruits Nm23-H1 to facilitate dynamin-mediated endocytosis during adherens junctions disassembly. Nature Cell Biology 4:929-936. doi: 10.1038/ncb881
30. Raftopoulou M, Hall A. 2004. Cell migration: rho GTPases lead the way. Developmental Biology 265:23-32. doi:10.1016/j.ydbio.2003.06.003
31. Ridley AJ, Paterson HF, Johnston CL, Diekmann D, Hall A. 1992. The small GTP-binding protein rac regulates growth factor-induced membrane ruffling. Cell 70:401-410. doi: 10.1016/0092-8674(92)90164-8
32. Rossman KL, Der CJ, Sondek J. 2005. GEF means go: turning on RHO GTPases with guanine nucleotide-exchange factors. Nature Reviews Molecular Cell Biology 6:167-180. doi: 10.1038/nrm1587
33. Suzuki S, Tanaka T, Poyurovsky MV, Nagano H, Mayama T, Ohkubo S, Lokshin M, Hosokawa H, Nakayama T, Suzuki Y, Sugano S, Sato E, Nagao T, Yokote K, Tatsuno I, Prives C. 2010. Phosphate-activated glutaminase (gLS2), a p53-inducible regulator of glutamine metabolism and reactive oxygen species. Proceedings of the National Academy of Sciences 107:7461-7466. doi: 10.1073/pnas.1002459107
34. Tang Z-Y. 2001. Hepatocellular carcinoma-cause, treatment and metastasis. World Journal of Gastroenterology 7:445-454. doi: 10.3748/wjg.v7.i4.445
35. Thangavelu K, Pan CQ, Karlberg T, Balaji G, Uttamchandani M, Suresh V, Schuler H, Low BC, Sivaraman J. 2012. Structural basis for the allosteric inhibitory mechanism of human kidney-type glutaminase (kGA) and its regulation by raf-mek-erk signaling in cancer cell metabolism. Proceedings of the National Academy of Sciences of the United States of America 109:7705-7710. doi: 10.1073/pnas.1116573109
36. Uka K, Aikata H, Takaki S, Shirakawa H, Jeong SC, Yamashina K, Hiramatsu A, Kodama H, Takahashi S, Chayama K. 2007. Clinical features and prognosis of patients with extrahepatic metastases from hepatocellular carcinoma. World Journal of Gastroenterology 13:414-420. doi: 10.3748/wjg.v13.i3.414
37. van Hennik PB, Klooster Jean Paul ten, Halstead JR, Voermans C, Anthony EC, Divecha N, Hordijk PL. 2003. The c-terminal domain of Rac1 contains two motifs that control targeting and signaling specificity. Journal of Biological Chemistry 278:39166-39175. doi: 10.1074/jbc.M307001200
38. Vetter IR, Wittinghofer A. 2001. The guanine nucleotide-binding switch in three dimensions. Science 294:1299-1304. doi: 10.1126/science.1062023
39. Vousden KH, Prives C. 2009. Blinded by the light: the growing complexity of p53. Cell 137:413-431. doi: 10.1016/j.cell.2009.04.037
40. Wang J-B, Erickson JW, Fuji R, Ramachandran S, Gao P, Dinavahi R, Wilson KF, Ambrosio ALB, Dias SMG, Dang CV, Cerione RA. 2010. Targeting mitochondrial glutaminase activity inhibits oncogenic transformation. Cancer Cell 18:207-219. doi: 10.1016/j.ccr.2010.08.009
41. Ward PS, Thompson CB. 2012. Metabolic reprogramming: a cancer hallmark even warburg did not anticipate. Cancer Cell 21:297-308. doi: 10.1016/j.ccr.2012.02.014
42. Worthylake DK, Rossman KL, Sondek J. 2000. Crystal structure of Rac1 in complex with the guanine nucleotide exchange region of Tiam1. Nature 408:682-688. doi: 10.1038/35047014
43. Xiang Y, Stine ZE, Xia J, Lu Y, O’Connor RS, Altman BJ, Hsieh AL, Gouw AM, Thomas AG, Gao P, Sun L, Song L, Yan B, Slusher BS, Zhuo J, Ooi LL, Lee CGL, Mancuso A, McCallion AS, Le A, Milone MC, Rayport S, Felsher DW, Dang CV. 2015. Targeted inhibition of tumor-specific glutaminase diminishes cell-autonomous tumorigenesis. Journal of Clinical Investigation 125:2293-2306. doi: 10.1172/JCI75836
44. Yue X, Zhao Y, Liu J, Zhang C, Yu H, Wang J, Zheng T, Liu L, Li J, Feng Z, Hu W. 2015. BAG2 promotes tumorigenesis through enhancing mutant p53 protein levels and function. eLife 4:e08401. doi: 10.7554/eLife.08401
45. Zhang C, Liu J, Liang Y, Wu R, Zhao Y, Hong X, Lin M, Yu H, Liu L, Levine AJ, Hu W, Feng Z. 2013. Tumour-associated mutant p53 drives the warburg effect. Nature Communications 4. doi: 10.1038/ncomms3935
46. Zhao Y, Zhang C, Yue X, Li X, Liu J, Yu H, Belyi VA, Yang Q, Feng Z, Hu W. 2015. Pontin, a new mutant p53-binding protein, promotes gain-of-function of mutant p53. Cell Death and Differentiation 22:1824-1836. doi:10.1038/cdd.2015.33
47. Zheng T, Wang J, Zhao Y, Zhang C, Lin M, Wang X, Yu H, Liu L, Feng Z, Hu W. 2013. Spliced MDM2 isoforms promote mutant p53 accumulation and gain-of-function in tumorigenesis. Nature Communications 4. doi: 10.1038/ncomms3996