Arrested cell proliferation through cysteine protease activity of eukaryotic ribosomal protein S4

Madasu, Yadaiah; Sudhamalla, Babu; Rao, P. Nageswara; Roy, Kunal; Ramakrishna, Dasari; Syed, Gulam Hussain; Konakanchi, Ramaiah; Bhuyan, Abani K.

doi:10.1096/fj.12-217752

Cited by 3 publications

(4 citation statements)

References 38 publications

(32 reference statements)

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“…Ribosomal proteins play extra-ribosomal roles in cell proliferation, cell cycle progression, and RNA transcription 1 – 3 . RPS26 is a highly conserved ribosomal protein with about 86.5% similarity in eukaryotes.…”

Section: Introductionmentioning

confidence: 88%

Loss of oocyte Rps26 in mice arrests oocyte growth and causes premature ovarian failure

Liu

Yan

et al. 2018

Cell Death Dis

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Global transcriptional activity increases as oocytes grow and is silenced in fully grown oocytes. Thus, the chromatin configuration varies during oocyte growth, but the molecular mechanisms regulating these changes remain to be clarified. Here, we studied a susceptibility gene of polycystic ovary syndrome (PCOS), RPS26, which is a ribosomal protein-encoding gene that is highly expressed in the ovary, but the functions of which remain unknown. Specific knockout of Rps26 in mouse oocytes resulted in retarded follicle development from pre-antral follicles to antral follicles, while the chromatin configurations of the oocytes were arrested at the transition from the non-surrounded nucleolus (NSN) to surrounded nucleolus (SN)-type. As a consequence, all oocytes died by postnatal day 84 resulting in premature ovarian failure (POF). Loss of Rps26 in oocytes led to decreased mRNA transcription and low levels of histone trimethylation on H3K4/H3K9 and DNA methylation at 5-cytosine, high levels of which are required for oocytes to transform from NSN to SN-type. Low protein levels of oocyte-derived growth differentiation factor 9, bone morphogenetic protein 15, and the oocyte-granulosa cell gap junction protein connexin 37 inhibited oocyte growth and retarded follicle development. The disruption of the phosphoinositide 3-kinase/protein kinase B/Forkhead box O-3a pathway contributed to oocyte death and follicle atresia. These results provide genetic clues for the clinical diagnosis of POF, especially in PCOS patients without treatment.

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Section: Introductionmentioning

confidence: 88%

Loss of oocyte Rps26 in mice arrests oocyte growth and causes premature ovarian failure

Liu

Yan

et al. 2018

Cell Death Dis

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“…In addition to rRNA, p53 also regulates the transcription of RP genes . For instance, p53 directly induces the expression of an RP, S27L,…”

Section: Ribosomal Proteins and Nucleolar Stressmentioning

confidence: 99%

“…Knockin mice with mutations in all five phosphorylatable sites have been produced, and have provided further insights into the phosphorylation events . As a key player in glucose homeostasis in mice, S6 phosphorylation is necessary for regulating this process in some cell types (pancreatic β‐cells and MEFs), but is expendable for the translational control of 5′‐TOP mRNAs …”

Section: Ribosomal Proteins and Nucleolar Stressmentioning

confidence: 99%

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Ribosomal Proteins and Human Diseases: Pathogenesis, Molecular Mechanisms, and Therapeutic Implications

Wang

Nag

Zhang

et al. 2014

Medicinal Research Reviews

179

154

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Ribosomes are essential components of the protein synthesis machinery. The process of ribosome biogenesis is well organized and tightly regulated. Recent studies have shown that ribosomal proteins (RPs) have extraribosomal functions that are involved in cell proliferation, differentiation, apoptosis, DNA repair, and other cellular processes. The dysfunction of RPs has been linked to the development and progression of hematological, metabolic, and cardiovascular diseases and cancer. Perturbation of ribosome biogenesis results in ribosomal stress, which triggers activation of the p53 signaling pathway through RPs-MDM2 interactions, resulting in p53-dependent cell cycle arrest and apoptosis. RPs also regulate cellular functions through p53-independent mechanisms. We herein review the recent advances in several forefronts of RP research, including the understanding of their biological features and roles in regulating cellular functions, maintaining cell homeostasis, and their involvement in the pathogenesis of human diseases. We also highlight the translational potential of this research for the identification of molecular biomarkers, and in the discovery and development of novel treatments for human diseases.

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Enzyme dimension of the ribosomal protein S4 across plant and animal kingdoms

Sudhamalla

Kumar

et al. 2013

Biochimica et Biophysica Acta (BBA) - General Subjects

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Arrested cell proliferation through cysteine protease activity of eukaryotic ribosomal protein S4

Cited by 3 publications

References 38 publications

Loss of oocyte Rps26 in mice arrests oocyte growth and causes premature ovarian failure

Loss of oocyte Rps26 in mice arrests oocyte growth and causes premature ovarian failure

Ribosomal Proteins and Human Diseases: Pathogenesis, Molecular Mechanisms, and Therapeutic Implications

Enzyme dimension of the ribosomal protein S4 across plant and animal kingdoms

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