Skp1-Cullin-F-box (SCF)-type ubiquitin ligase FBXW7 negatively regulates spermatogonial stem cell self-renewal

Kanatsu-Shinohara, Mito; Onoyama, Ichiro; Nakayama, Keiichi I.; Shinohara, Takashi

doi:10.1073/pnas.1401837111

Cited by 72 publications

(46 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It has also been suggested that Pin1 overexpression in cancers destabilizes Fbw7 by directly generating Fbw7 monomers that are targeted for degradation through enhanced autoubiquitylation (Min et al, 2012). However, two other studies have disputed these findings (Kanatsu-Shinohara et al, 2014; Welcker et al, 2013). …”

Section: Additional Mechanisms Of Fbw7 Disruption In Cancermentioning

confidence: 98%

Tumor Suppression by the Fbw7 Ubiquitin Ligase: Mechanisms and Opportunities

2014

View full text Add to dashboard Cite

Summary Tumor suppressors with widespread impact on carcinogenesis control broad spectra of oncogenic pathways. Protein degradation is an emerging mechanism by which tumor suppressors regulate a diversity of pathways and is exemplified by the SCFFbw7 ubiquitin ligase. Rapidly accumulating data indicate that SCFFbw7 regulates a network of crucial oncoproteins. Importantly, the FBXW7 gene, which encodes Fbw7, is one of the most frequently mutated genes in human cancers. These studies are yielding important new insights into tumorigenesis and may soon enable therapies targeting the Fbw7 pathway. Here, we focus on the mechanisms and consequences of Fbw7 deregulation in cancers and discuss possible therapeutic approaches.

show abstract

Section: Additional Mechanisms Of Fbw7 Disruption In Cancermentioning

confidence: 98%

Tumor Suppression by the Fbw7 Ubiquitin Ligase: Mechanisms and Opportunities

2014

View full text Add to dashboard Cite

show abstract

“…To our knowledge, this is the first report of increased SSC activity in knockout mice. Investigation of other negative regulators that may counteract self-renewal signals will deepen our knowledge of SSC biology (Kanatsu-Shinohara et al 2014).…”

Section: Perspectives and Concluding Remarksmentioning

confidence: 99%

Regulation of spermatogonial stem cell self-renewal and spermatocyte meiosis by Sertoli cell signaling

Chen¹,

Liu²

2015

Reproduction

235

166

View full text Add to dashboard Cite

Spermatogenesis is a continuous and productive process supported by the self-renewal and differentiation of spermatogonial stem cells (SSCs), which arise from undifferentiated precursors known as gonocytes and are strictly controlled in a special 'niche' microenvironment in the seminiferous tubules. Sertoli cells, the only somatic cell type in the tubules, directly interact with SSCs to control their proliferation and differentiation through the secretion of specific factors. Spermatocyte meiosis is another key step of spermatogenesis, which is regulated by Sertoli cells on the luminal side of the blood-testis barrier through paracrine signaling. In this review, we mainly focus on the role of Sertoli cells in the regulation of SSC self-renewal and spermatocyte meiosis, with particular emphasis on paracrine and endocrine-mediated signaling pathways. Sertoli cell growth factors, such as glial cell line-derived neurotrophic factor (GDNF) and fibroblast growth factor 2 (FGF2), as well as Sertoli cell transcription factors, such as ETS variant 5 (ERM; also known as ETV5), nociceptin, neuregulin 1 (NRG1), and androgen receptor (AR), have been identified as the most important upstream factors that regulate SSC self-renewal and spermatocyte meiosis. Other transcription factors and signaling pathways (GDNF-RET-GFRA1 signaling, FGF2-MAP2K1 signaling, CXCL12-CXCR4 signaling, CCL9-CCR1 signaling, FSH-nociceptin/OPRL1, retinoic acid/FSH-NRG/ERBB4, and AR/RB-ARID4A/ARID4B) are also addressed.Reproduction (2015) 149 R159-R167

show abstract

“…We reported previously that Myc/Mycn overexpression increases the SSC activity of fresh testis cells (Kanatsu-Shinohara et al 2014). To evaluate the function of Myc/ Mycn, we produced conditional knockout mice with floxed alleles for Myc or Mycn (Myc f/f or Mycn f/f ).…”

Section: Reduced Self-renewal Division Of Myc Double-knockout Testis mentioning

confidence: 99%

“…We previously found that Fbxw7 ubiquitin ligase deficiency induces active proliferation of SSCs in vitro by increasing MYC expression (Kanatsu-Shinohara et al 2014). While shRNAmediated Myc depletion decreased colonization of SSCs upon transplantation, Myc overexpression in pup testis culture increased the concentration of SSCs, suggesting that Myc increases the frequency of self-renewal division.…”

mentioning

confidence: 98%

Myc/Mycn-mediated glycolysis enhances mouse spermatogonial stem cell self-renewal

et al. 2016

Self Cite

View full text Add to dashboard Cite

Myc plays critical roles in the self-renewal division of various stem cell types. In spermatogonial stem cells (SSCs), Myc controls SSC fate decisions because Myc overexpression induces enhanced self-renewal division, while depletion of Max, a Myc-binding partner, leads to meiotic induction. However, the mechanism by which Myc acts on SSC fate is unclear. Here we demonstrate a critical link between Myc/Mycn gene activity and glycolysis in SSC selfrenewal. In SSCs, Myc/Mycn are regulated by Foxo1, whose deficiency impairs SSC self-renewal. Myc/Mycn-deficient SSCs not only undergo limited self-renewal division but also display diminished glycolytic activity. While inhibition of glycolysis decreased SSC activity, chemical stimulation of glycolysis or transfection of active Akt1 or Pdpk1 (phosphoinositide-dependent protein kinase 1 ) augmented self-renewal division, and long-term SSC cultures were derived from a nonpermissive strain that showed limited self-renewal division. These results suggested that Myc-mediated glycolysis is an important factor that increases the frequency of SSC self-renewal division.

show abstract

Skp1-Cullin-F-box (SCF)-type ubiquitin ligase FBXW7 negatively regulates spermatogonial stem cell self-renewal

Cited by 72 publications

References 34 publications

Tumor Suppression by the Fbw7 Ubiquitin Ligase: Mechanisms and Opportunities

Tumor Suppression by the Fbw7 Ubiquitin Ligase: Mechanisms and Opportunities

Regulation of spermatogonial stem cell self-renewal and spermatocyte meiosis by Sertoli cell signaling

Myc/Mycn-mediated glycolysis enhances mouse spermatogonial stem cell self-renewal

Contact Info

Product

Resources

About