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p62/SQSTM1 Cooperates with Hyperactive mTORC1 to Regulate Glutathione Production, Maintain Mitochondrial Integrity, and Promote Tumorigenesis.

Lam HC, Baglini CV, Lope AL, Parkhitko AA, Liu HJ, Alesi N, Malinowska IA, Ebrahimi-Fakhari D, Saffari A, Yu JJ, Pereira A, Khabibullin D, Ogorek B, Nijmeh J, Kavanagh T, Handen A, Chan SY, Asara JM, Oldham WM, Diaz-Meco MT, Moscat J, Sahin M, Priolo C, Henske EP.

Cancer Res. 2017 Jun 15;77(12):3255-3267. doi: 10.1158/0008-5472.CAN-16-2458. Epub 2017 May 16.


Tumorigenesis in tuberous sclerosis complex is autophagy and p62/sequestosome 1 (SQSTM1)-dependent.

Parkhitko A, Myachina F, Morrison TA, Hindi KM, Auricchio N, Karbowniczek M, Wu JJ, Finkel T, Kwiatkowski DJ, Yu JJ, Henske EP.

Proc Natl Acad Sci U S A. 2011 Jul 26;108(30):12455-60. doi: 10.1073/pnas.1104361108. Epub 2011 Jul 11.


High-throughput drug screen identifies chelerythrine as a selective inducer of death in a TSC2-null setting.

Medvetz D, Sun Y, Li C, Khabibullin D, Balan M, Parkhitko A, Priolo C, Asara JM, Pal S, Yu J, Henske EP.

Mol Cancer Res. 2015 Jan;13(1):50-62. doi: 10.1158/1541-7786.MCR-14-0440. Epub 2014 Sep 3.


Autophagy-dependent metabolic reprogramming sensitizes TSC2-deficient cells to the antimetabolite 6-aminonicotinamide.

Parkhitko AA, Priolo C, Coloff JL, Yun J, Wu JJ, Mizumura K, Xu W, Malinowska IA, Yu J, Kwiatkowski DJ, Locasale JW, Asara JM, Choi AM, Finkel T, Henske EP.

Mol Cancer Res. 2014 Jan;12(1):48-57. doi: 10.1158/1541-7786.MCR-13-0258-T. Epub 2013 Dec 2.


Therapeutic targeting of cellular metabolism in cells with hyperactive mTORC1: a paradigm shift.

Medvetz D, Priolo C, Henske EP.

Mol Cancer Res. 2015 Jan;13(1):3-8. doi: 10.1158/1541-7786.MCR-14-0343. Epub 2014 Oct 8. Review.


Synthetic lethality of combined glutaminase and Hsp90 inhibition in mTORC1-driven tumor cells.

Li J, Csibi A, Yang S, Hoffman GR, Li C, Zhang E, Yu JJ, Blenis J.

Proc Natl Acad Sci U S A. 2015 Jan 6;112(1):E21-9. doi: 10.1073/pnas.1417015112. Epub 2014 Dec 18.


mTORC1 enhancement of STIM1-mediated store-operated Ca2+ entry constrains tuberous sclerosis complex-related tumor development.

Peng H, Liu J, Sun Q, Chen R, Wang Y, Duan J, Li C, Li B, Jing Y, Chen X, Mao Q, Xu KF, Walker CL, Li J, Wang J, Zhang H.

Oncogene. 2013 Sep 26;32(39):4702-11. doi: 10.1038/onc.2012.481. Epub 2012 Oct 29.


Pivotal role of augmented αB-crystallin in tumor development induced by deficient TSC1/2 complex.

Wang F, Chen X, Li C, Sun Q, Chen Y, Wang Y, Peng H, Liu Z, Chen R, Liu K, Yan H, Ye BH, Kwiatkowski DJ, Zhang H.

Oncogene. 2014 Aug 21;33(34):4352-8. doi: 10.1038/onc.2013.401. Epub 2013 Sep 30.


Tuberin activates and controls the distribution of Rac1 via association with p62 and ubiquitin through the mTORC1 signaling pathway.

Okura H, Kobayashi T, Koike M, Ohsawa M, Zhang D, Arai H, Uchiyama Y, Hino O.

Int J Oncol. 2013 Aug;43(2):447-56. doi: 10.3892/ijo.2013.1984. Epub 2013 Jun 12.


mTOR Hyperactivation by Ablation of Tuberous Sclerosis Complex 2 in the Mouse Heart Induces Cardiac Dysfunction with the Increased Number of Small Mitochondria Mediated through the Down-Regulation of Autophagy.

Taneike M, Nishida K, Omiya S, Zarrinpashneh E, Misaka T, Kitazume-Taneike R, Austin R, Takaoka M, Yamaguchi O, Gambello MJ, Shah AM, Otsu K.

PLoS One. 2016 Mar 29;11(3):e0152628. doi: 10.1371/journal.pone.0152628. eCollection 2016.


Mourning Dr. Alfred G. Knudson: the two-hit hypothesis, tumor suppressor genes, and the tuberous sclerosis complex.

Hino O, Kobayashi T.

Cancer Sci. 2017 Jan;108(1):5-11. doi: 10.1111/cas.13116. Epub 2017 Jan 23. Review.


TSC2 Deficiency Unmasks a Novel Necrosis Pathway That Is Suppressed by the RIP1/RIP3/MLKL Signaling Cascade.

Filipczak PT, Thomas C, Chen W, Salzman A, McDonald JD, Lin Y, Belinsky SA.

Cancer Res. 2016 Dec 15;76(24):7130-7139. Epub 2016 Oct 18.


Complex Neurological Phenotype in Mutant Mice Lacking Tsc2 in Excitatory Neurons of the Developing Forebrain(123).

Crowell B, Lee GH, Nikolaeva I, Dal Pozzo V, D'Arcangelo G.

eNeuro. 2015 Oct 22;2(6). pii: ENEURO.0046-15.2015. doi: 10.1523/ENEURO.0046-15.2015. eCollection 2015 Nov-Dec.


mTORC1-Driven Tumor Cells Are Highly Sensitive to Therapeutic Targeting by Antagonists of Oxidative Stress.

Li J, Shin S, Sun Y, Yoon SO, Li C, Zhang E, Yu J, Zhang J, Blenis J.

Cancer Res. 2016 Aug 15;76(16):4816-27. doi: 10.1158/0008-5472.CAN-15-2629. Epub 2016 May 17.


mTORC1-mediated downregulation of COX2 restrains tumor growth caused by TSC2 deficiency.

Li H, Jin F, Jiang K, Ji S, Wang L, Ni Z, Chen X, Hu Z, Zhang H, Liu Y, Qin Y, Zha X.

Oncotarget. 2016 May 10;7(19):28435-47. doi: 10.18632/oncotarget.8633.


Differential IKK/NF-κB Activity Is Mediated by TSC2 through mTORC1 in PTEN-Null Prostate Cancer and Tuberous Sclerosis Complex Tumor Cells.

Gao Y, Gartenhaus RB, Lapidus RG, Hussain A, Zhang Y, Wang X, Dan HC.

Mol Cancer Res. 2015 Dec;13(12):1602-14. doi: 10.1158/1541-7786.MCR-15-0213. Epub 2015 Sep 15.


Tuberous sclerosis complex inactivation disrupts melanogenesis via mTORC1 activation.

Cao J, Tyburczy ME, Moss J, Darling TN, Widlund HR, Kwiatkowski DJ.

J Clin Invest. 2017 Jan 3;127(1):349-364. doi: 10.1172/JCI84262. Epub 2016 Dec 5.


Prolonging the survival of Tsc2 conditional knockout mice by glutamine supplementation.

Rozas NS, Redell JB, McKenna J 3rd, Moore AN, Gambello MJ, Dash PK.

Biochem Biophys Res Commun. 2015 Feb 20;457(4):635-9. doi: 10.1016/j.bbrc.2015.01.039. Epub 2015 Jan 19.


Impaired Mitochondrial Dynamics and Mitophagy in Neuronal Models of Tuberous Sclerosis Complex.

Ebrahimi-Fakhari D, Saffari A, Wahlster L, Di Nardo A, Turner D, Lewis TL Jr, Conrad C, Rothberg JM, Lipton JO, Kölker S, Hoffmann GF, Han MJ, Polleux F, Sahin M.

Cell Rep. 2016 Oct 18;17(4):1053-1070. doi: 10.1016/j.celrep.2016.09.054. Erratum in: Cell Rep. 2016 Nov 15;17 (8):2162.


Neuronal Tsc1/2 complex controls autophagy through AMPK-dependent regulation of ULK1.

Di Nardo A, Wertz MH, Kwiatkowski E, Tsai PT, Leech JD, Greene-Colozzi E, Goto J, Dilsiz P, Talos DM, Clish CB, Kwiatkowski DJ, Sahin M.

Hum Mol Genet. 2014 Jul 15;23(14):3865-74. doi: 10.1093/hmg/ddu101. Epub 2014 Mar 5.

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