ARD1 Stabilization of TSC2 Suppresses Tumorigenesis Through the mTOR Signaling Pathway

Hsu-Ping Kuo, Dung-Fang Lee, Chun-Te Chen, Mo Liu, Chao-Kai Chou, Hong-Jen Lee, Yi Du, Xiaoming Xie, Yongkun Wei, Weiya Xia, Zhang Weihua, Jer-Yen Yang, Chia-Jui Yen, Tzu-Hsuan Huang, Minjia Tan, Gang Xing, Yingming Zhao, Chien-Hsing Lin, Shih-Feng Tsai, Isaiah J. Fidler, Mien-Chie Hung*

*To whom correspondence should be addressed. E-mail: mhung{at}mdanderson.org

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• Fig. S1. Lower copy number of genomic ARD1 was found in ARD1 LOH group.
• Fig. S2. Endogenous ARD1 in five cell lines with low ARD1 abundance and five cell lines with high ARD1 abundance.
• Fig. S3. Myc-ARD1 had a stronger growth-inhibitory effect in tumor cells with lower endogenous ARD1 than in cells with abundant endogenous ARD1.
• Fig. S4. Knockdown of ARD1 with either of two different siRNAs increased the growth of MDA-MB-435 cells.
• Fig. S5. ARD1 reduced the degree of pS6K1(T389) whereas depletion of ARD1 increased pS6K1(T389) under conditions of both serum starvation and insulin-like growth factor (IGF) stimulation.
• Fig. S6. ARD1 reduced p4EBP1(S65) under conditions of both serum starvation and IGF stimulation.
• Fig. S7. Transient transfection of Myc-ARD1 increased the amount of TSC2 in HEK293T cells.
• Fig. S8. Depletion of ARD1 decreased the stability of TSC2.
• Fig. S9. The data of Fig. 6B on a semilog plot.
• Fig. S10. Treatment of MG132 increased TSC2 abundance.
• Fig. S11. Schematic shows wild-type (WT) ARD1 and three truncated forms of ARD1.
• Fig. S12. WT ARD1, but not ARD1 ΔC, increased the stability of TSC2.
• Fig. S13. WT ARD1, but not ARD1 AA or ARD1 ΔAT, stabilized TSC2.
• Fig. S14. WT ARD1, but not ARD1 AA or ARD1 ΔAT, reduced ubiquitination of TSC2.
• Fig. S15. WT ARD1, but not ARD1 AA or ARD1 ΔAT, significantly suppressed the growth of MDA-MB-435 and MCF-7 cells.
• Fig. S16. Depletion of ARD1 decreased the acetylation of endogenous TSC2.
• Fig. S17. We detected no ARD1-induced ε-acetylation of TSC2.
• Fig. S18. Shown are two representative breast cancer specimens with consecutive sections.
• Fig. S19. Representative images of ARD1 and TSC2 abundance in four different types of cancers.
• Table S1. Relationship between ARD1 and TSC2 in surgical specimens of various tumors.

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