Aggregation of Ribosomal Protein S6 at Nucleolus Is Cell Cycle‐Controlled and Its Function in Pre‐rRNA Processing Is Phosphorylation Dependent

Zhang, Duo; Chen, Huipeng; Duan, Haifeng; Gao, Lihua; Shao, Yimin; Chen, Ke-Yan; Wang, Youliang; Lan, Fenghua; Hu, Xianwen

doi:10.1002/jcb.25458

Cited by 10 publications

(9 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The rationale for this assay is based on the observation that defects if biogenesis pathway can cause ribosomal subunit export defects 80, 81 . Rps6 is an early assembling 40S subunit ribosomal protein 82–84 , allowing us to score early defects in 40S synthesis. Indeed, we found an accumulation of RPS6 in the nucleus in Pex5 RNAi oenocytes, after normalized to total intensity (Fig.…”

Section: Resultsmentioning

confidence: 99%

Peroxisome import stress impairs ribosome biogenesis and induces integrative stress response through eIF2α phosphorylation

Huang

Bai

2020

Preprint

View full text Add to dashboard Cite

Peroxisome biogenesis diseases (PBDs) are characterized by global defects in peroxisomal function and can result in severe brain, liver, kidney, and bone malfunctions. PBDs are due to mutations in peroxisome biogenesis factors (PEX genes) that are responsible for peroxisome assembly and function. There is increasing evidence suggesting that peroxisome import functions decline during aging. The transcriptome profiling of peroxisome import defects is still lacking. To identify conserved responses, we undertook a bioinformatic transcriptomic analysis on Drosophila oenocyte specific Pex1, Pex12 and Pex5 knockdowns. In addition, we performed analysis on human cells with induced peroxisome import stress. We uncovered that oenocyte-specific Pex1, Pex12 and Pex5 have distinct transcriptional profiles with each other. Using gene set enrichment analysis (GSEA), we identified protein processing in endoplasmic reticulum pathway, specifically ER-associated protein degradation (ERAD) pathway is enriched and induced in all PEX knockdowns in Drosophila. Moreover, we uncovered decreased expression in ribosome biogenesis genes in flies and human cells. Indeed, we identified a stall at the 5’-ETS cleavage sites during the ribosome biogenesis and impaired 40S small ribosomal export in both flies and human. Our data indicates an unexpected link between peroxisome and ribosome biogenesis. Our results suggest that reduced ribosome biogenesis could be conserved cellular response to reduce peroxisome import stress.

show abstract

Section: Resultsmentioning

confidence: 99%

Peroxisome import stress impairs ribosome biogenesis and induces integrative stress response through eIF2α phosphorylation

Huang

Bai

2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Cyclic accumulation of RPS6 in the nucleolus, in accordance with the cell cycle, has been reported; it starts in the S phase, culminates in the G 2 phase, and diminishes in the M phase with the disintegration of the nucleoli [ 327 ]. In addition, mammalian RPS6 is dephosphorylated upon heat shock [ 328 , 329 ].…”

Section: Regulation Of Rps6mentioning

confidence: 99%

“…However, the hepatic hypertrophy but not hyperplasia in fasted animals in response to nutrients was not blocked by the absence of RPS6. A recent study has demonstrated that p-RPS6 is involved in the endonuclease processing of 30S pre-rRNAs in the nucleolus [ 327 ]. The splicing of 30S pre-rRNAs was only mediated by fully phosphorylated RPS6 in the C-terminal five serine residues.…”

Section: Functions Of Rps6mentioning

confidence: 99%

Ribosomal Protein S6: A Potential Therapeutic Target against Cancer?

You

Park

et al. 2021

IJMS

View full text Add to dashboard Cite

Ribosomal protein S6 (RPS6) is a component of the 40S small ribosomal subunit and participates in the control of mRNA translation. Additionally, phospho (p)-RPS6 has been recognized as a surrogate marker for the activated PI3K/AKT/mTORC1 pathway, which occurs in many cancer types. However, downstream mechanisms regulated by RPS6 or p-RPS remains elusive, and the therapeutic implication of RPS6 is underappreciated despite an approximately half a century history of research on this protein. In addition, substantial evidence from RPS6 knockdown experiments suggests the potential role of RPS6 in maintaining cancer cell proliferation. This motivates us to investigate the current knowledge of RPS6 functions in cancer. In this review article, we reviewed the current information about the transcriptional regulation, upstream regulators, and extra-ribosomal roles of RPS6, with a focus on its involvement in cancer. We also discussed the therapeutic potential of RPS6 in cancer.

show abstract

“…Activated p53 then transactivates its downstream targets to induce growth arrest and apoptosis to block tumorigenesis. (Adilakshmi and Laine, 2002;Bai et al, 2014;Barlow et al, 2010a;He and Sun, 2007;Jang et al, 2012a;Jeon et al, 2008;Khanna et al, 2003;Li et al, 2010;Naora et al, 1998;Neumann and Krawinkel, 1997;Russo et al, 2013;Takagi et al, 2005;Wu et al, 2012;Yang et al, 2012;Zhu et al, 2009) Cell cycle S3, S5, S6, S7, S14, S15, S19, S20, S25, S26, S27, S27L, S27a, L3, L5, L6, L7, L11, L13, L23, L26, L31, L34, L37, L41 (Cui et al, 2014;Daftuar et al, 2013;Dai et al, , 2007bGao et al, 2013;Gou et al, 2010;Iadevaia et al, 2010;Kobayashi et al, 2006;Maruyama et al, 2014;Matragkou et al, 2008;Moorthamer and Chaudhuri, 1999;Neumann and Krawinkel, 1997;Russo et al, 2013;Sun et al, 2011;Takagi et al, 2005;Wang et al, 2011a;Wanzel et al, 2008;Xiong et al, 2011;Zhang et al, 2013Zhang et al, , 2015Zhou et al, 2013a) Cell proliferation S6, S9, S13, S14, S15a, S24, S27, L6, L8, L11, L15, L17, L26, L29, L31, L34, L36a (Dai et al, 2007a;Gou et al, 2010Kim et al, 2004;Li et al, 2010…”

Section: Apoptosismentioning

confidence: 99%

The role of ribosomal proteins in the regulation of cell proliferation, tumorigenesis, and genomic integrity

Xiong

Sun

2016

Sci. China Life Sci.

109

View full text Add to dashboard Cite

Ribosomal proteins (RPs), the essential components of the ribosome, are a family of RNA-binding proteins, which play prime roles in ribosome biogenesis and protein translation. Recent studies revealed that RPs have additional extra-ribosomal functions, independent of protein biosynthesis, in regulation of diverse cellular processes. Here, we review recent advances in our understanding of how RPs regulate apoptosis, cell cycle arrest, cell proliferation, neoplastic transformation, cell migration and invasion, and tumorigenesis through both MDM2/p53-dependent and p53-independent mechanisms. We also discuss the roles of RPs in the maintenance of genome integrity via modulating DNA damage response and repair. We further discuss mutations or deletions at the somatic or germline levels of some RPs in human cancers as well as in patients of Diamond-Blackfan anemia and 5q-syndrome with high susceptibility to cancer development. Moreover, we discuss the potential clinical application, based upon abnormal levels of RPs, in biomarker development for early diagnosis and/or prognosis of certain human cancers. Finally, we discuss the pressing issues in the field as future perspectives for better understanding the roles of RPs in human cancers to eventually benefit human health. ribosomal protein, tumorigenesis, genomic integrity, ribosomal stress, p53, MDM2 Citation:Xu, X., Xiong, X., and Sun, Y. (2016). The role of ribosomal proteins in the regulation of cell proliferation, tumorigenesis, and genomic integrity. Sci China Life Sci 59, 656 -672.

show abstract

Aggregation of Ribosomal Protein S6 at Nucleolus Is Cell Cycle‐Controlled and Its Function in Pre‐rRNA Processing Is Phosphorylation Dependent

Cited by 10 publications

References 45 publications

Peroxisome import stress impairs ribosome biogenesis and induces integrative stress response through eIF2α phosphorylation

Peroxisome import stress impairs ribosome biogenesis and induces integrative stress response through eIF2α phosphorylation

Ribosomal Protein S6: A Potential Therapeutic Target against Cancer?

The role of ribosomal proteins in the regulation of cell proliferation, tumorigenesis, and genomic integrity

Contact Info

Product

Resources

About