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Sci. Signal., 8 January 2013
Vol. 6, Issue 257, p. ra3
Growth factors trigger the ubiquitination of the kinase Akt, which facilitates its activation. Yang et al. identified the tumor suppressor CYLD as a deubiquitinase (DUB) that inhibits Akt activity. CYLD associated with Akt under nutrient-deficient conditions and dissociated from Akt after growth factor stimulation. Compared to prostate cancer cells with CYLD, those that were deficient in CYLD showed increased glucose uptake and proliferation, processes that are enhanced by Akt activity, and developed into larger tumors when injected into mice. In individuals with primary prostate tumors, decreased abundance of CYLD correlated with increased activation of Akt. Thus, deubiquitination of Akt is required to reset its activity, and attenuation of Akt may contribute to the tumor-suppressive function of CYLD.
Citation: W.-L. Yang, G. Jin, C.-F. Li, Y. S. Jeong, A. Moten, D. Xu, Z. Feng, W. Chen, Z. Cai, B. Darnay, W. Gu, H.-K. Lin, Cycles of Ubiquitination and Deubiquitination Critically Regulate Growth Factor–Mediated Activation of Akt Signaling. Sci. Signal.6, ra3 (2013).
Yixin Yao, Milind Suraokar, Bryant G. Darnay, Brett G. Hollier, Tattym E. Shaiken, Takayuki Asano, Chien-Hung Chen, Benny H.-J. Chang, Yiling Lu, Gordon B. Mills, Dos Sarbassov, Sendurai A. Mani, James L. Abbruzzese, and Shrikanth A. G. Reddy (8 January 2013) Sci. Signal.6 (257), ra2.
[DOI: 10.1126/scisignal.2003295] |Editor's Summary »|Abstract »|Full Text »|PDF »|Supplementary Materials »
Nagalingam R. Sundaresan, Vinodkumar B. Pillai, Don Wolfgeher, Sadhana Samant, Prabhakaran Vasudevan, Vishwas Parekh, Hariharasundaram Raghuraman, John M. Cunningham, Madhu Gupta, and Mahesh P. Gupta (19 July 2011) Sci. Signal.4 (182), ra46.
[DOI: 10.1126/scisignal.2001465] |Editor's Summary »|Abstract »|Full Text »|PDF »|Supplementary Materials »
L. Bryan Ray (1 September 2009) Sci. Signal.2 (86), ec293.
[DOI: 10.1126/scisignal.286ec293] |Abstract »