Tags

Type your tag names separated by a space and hit enter

PICT-1 triggers a pro-death autophagy through inhibiting rRNA transcription and AKT/mTOR/p70S6K signaling pathway.
Oncotarget. 2016 Nov 29; 7(48):78747-78763.O

Abstract

PICT-1 was originally identified as a tumor suppressor. Here, we found that PICT-1 overexpression triggered pro-death autophagy without nucleolar disruption or p53 accumulation in U251 and MCF7 cells. Truncated PICT-1 fragments 181-346 and 1-346, which partly or totally lack nucleolar localization, showed weaker autophagy-inducing effects than full-length PICT-1 and a well-defined nucleolar mutant (181-479). Furthermore, PICT-1 partly localizes to the nucleolar fibrillar center (FC) and directly binds to ribosomal DNA (rDNA) gene loci, where it interacts with upstream binding factor (UBF). Overexpression of PICT-1 or the 181-479 mutant, but not the 1-346 or 181-346 mutants, markedly inhibited the phosphorylation of UBF and the recruitment of rRNA polymerase I (Pol I) to the rDNA promoter in response to serum stimulation, thereby suppressing rRNA transcription, suggesting that rRNA transcription inhibition might be an important contributor to PICT-1-induced autophagy. This is supported by the finding that CX-5461, a specific Pol I inhibitor, also induced autophagy. In addition, both CX-5461 and PICT-1, but not the 1-346 or 181-346 mutants, significantly suppressed the activation of the Akt/mTOR/p70S6K signaling pathway. Our data show that PICT-1 triggers pro-death autophagy through inhibition of rRNA transcription and the inactivation of AKT/mTOR/p70S6K pathway, independent of nucleolar disruption and p53 activation.

Authors+Show Affiliations

The Shenzhen Key Lab of Gene and Antibody Therapy, Center for Biotechnology & Biomedicine, Division of Life and Health Sciences, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, China. School of Life Sciences, Tsinghua University, Beijing 100084, China.Key Laboratory of Plant Cell Activities and Stress Adaptation, Ministry of Education, School of Life Sciences, Lanzhou University, Lanzhou 730000, China.Department of Laboratory Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China.Department of Laboratory Medicine, The Fourth Affiliated Hospital of Guangzhou Medical University, Guangzhou 511447, China.The Shenzhen Key Laboratory of Gene and Antibody Therapy, Center for Biotechnology & Biomedicine, Division of Life and Health Sciences, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, China.The Shenzhen Key Laboratory of Gene and Antibody Therapy, Center for Biotechnology & Biomedicine, Division of Life and Health Sciences, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, China. School of Life Sciences, Tsinghua University, Beijing 100084, China.Department of Quality Inspection, Shenzhen Weiguang Biological Products Co., Ltd, Shenzhen 518107, China.Department of Quality Inspection, Shenzhen Weiguang Biological Products Co., Ltd, Shenzhen 518107, China.The Shenzhen Key Laboratory of Gene and Antibody Therapy, Center for Biotechnology & Biomedicine, Division of Life and Health Sciences, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, China.Key Laboratory of Plant Cell Activities and Stress Adaptation, Ministry of Education, School of Life Sciences, Lanzhou University, Lanzhou 730000, China.The Shenzhen Key Laboratory of Gene and Antibody Therapy, Center for Biotechnology & Biomedicine, Division of Life and Health Sciences, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, China. School of Life Sciences, Tsinghua University, Beijing 100084, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27729611

Citation

Chen, Hongbo, et al. "PICT-1 Triggers a Pro-death Autophagy Through Inhibiting rRNA Transcription and AKT/mTOR/p70S6K Signaling Pathway." Oncotarget, vol. 7, no. 48, 2016, pp. 78747-78763.
Chen H, Duo Y, Hu B, et al. PICT-1 triggers a pro-death autophagy through inhibiting rRNA transcription and AKT/mTOR/p70S6K signaling pathway. Oncotarget. 2016;7(48):78747-78763.
Chen, H., Duo, Y., Hu, B., Wang, Z., Zhang, F., Tsai, H., Zhang, J., Zhou, L., Wang, L., Wang, X., & Huang, L. (2016). PICT-1 triggers a pro-death autophagy through inhibiting rRNA transcription and AKT/mTOR/p70S6K signaling pathway. Oncotarget, 7(48), 78747-78763. https://doi.org/10.18632/oncotarget.12288
Chen H, et al. PICT-1 Triggers a Pro-death Autophagy Through Inhibiting rRNA Transcription and AKT/mTOR/p70S6K Signaling Pathway. Oncotarget. 2016 Nov 29;7(48):78747-78763. PubMed PMID: 27729611.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - PICT-1 triggers a pro-death autophagy through inhibiting rRNA transcription and AKT/mTOR/p70S6K signaling pathway. AU - Chen,Hongbo, AU - Duo,Yanhong, AU - Hu,Bo, AU - Wang,Zhiwei, AU - Zhang,Fang, AU - Tsai,Hsiangi, AU - Zhang,Jianping, AU - Zhou,Lanzhen, AU - Wang,Lijun, AU - Wang,Xinyu, AU - Huang,Laiqiang, PY - 2016/05/26/received PY - 2016/09/16/accepted PY - 2016/10/13/pubmed PY - 2018/2/24/medline PY - 2016/10/13/entrez KW - PICT-1 KW - autophagy KW - nucleolus KW - p53 KW - rRNA transcription SP - 78747 EP - 78763 JF - Oncotarget JO - Oncotarget VL - 7 IS - 48 N2 - PICT-1 was originally identified as a tumor suppressor. Here, we found that PICT-1 overexpression triggered pro-death autophagy without nucleolar disruption or p53 accumulation in U251 and MCF7 cells. Truncated PICT-1 fragments 181-346 and 1-346, which partly or totally lack nucleolar localization, showed weaker autophagy-inducing effects than full-length PICT-1 and a well-defined nucleolar mutant (181-479). Furthermore, PICT-1 partly localizes to the nucleolar fibrillar center (FC) and directly binds to ribosomal DNA (rDNA) gene loci, where it interacts with upstream binding factor (UBF). Overexpression of PICT-1 or the 181-479 mutant, but not the 1-346 or 181-346 mutants, markedly inhibited the phosphorylation of UBF and the recruitment of rRNA polymerase I (Pol I) to the rDNA promoter in response to serum stimulation, thereby suppressing rRNA transcription, suggesting that rRNA transcription inhibition might be an important contributor to PICT-1-induced autophagy. This is supported by the finding that CX-5461, a specific Pol I inhibitor, also induced autophagy. In addition, both CX-5461 and PICT-1, but not the 1-346 or 181-346 mutants, significantly suppressed the activation of the Akt/mTOR/p70S6K signaling pathway. Our data show that PICT-1 triggers pro-death autophagy through inhibition of rRNA transcription and the inactivation of AKT/mTOR/p70S6K pathway, independent of nucleolar disruption and p53 activation. SN - 1949-2553 UR - https://www.unboundmedicine.com/medline/citation/27729611/PICT_1_triggers_a_pro_death_autophagy_through_inhibiting_rRNA_transcription_and_AKT/mTOR/p70S6K_signaling_pathway_ L2 - http://www.impactjournals.com/oncotarget/misc/linkedout.php?pii=12288 DB - PRIME DP - Unbound Medicine ER -