Cell metabolism control through o-glcnacylation of stat5: A full or empty fuel tank makes a big difference for cancer cell growth and survival

Manuel Rauth, Patricia Freund, Anna Orlova, Stefan Grünert, Nikola Tasic, Xiaonan Han, Hai Bin Ruan, Heidi A. Neubauer, Richard Moriggl

Research output: Contribution to journalReview article

1 Scopus citations

Abstract

O-GlcNAcylation is a post-translational modification that influences tyrosine phosphorylation in healthy and malignant cells. O-GlcNAc is a product of the hexosamine biosynthetic pathway, a side pathway of glucose metabolism. It is essential for cell survival and proper gene regulation, mirroring the metabolic status of a cell. STAT3 and STAT5 proteins are essential transcription factors that can act in a mutational context-dependent manner as oncogenes or tumor suppressors. They regulate gene expression for vital processes such as cell differentiation, survival, or growth, and are also critically involved in metabolic control. The role of STAT3/5 proteins in metabolic processes is partly independent of their transcriptional regulatory role, but is still poorly understood. Interestingly, STAT3 and STAT5 are modified by O-GlcNAc in response to the metabolic status of the cell. Here, we discuss and summarize evidence of O-GlcNAcylation-regulating STAT function, focusing in particular on hyperactive STAT5A transplant studies in the hematopoietic system. We emphasize that a single O-GlcNAc modification is essential to promote development of neoplastic cell growth through enhancing STAT5A tyrosine phosphorylation. Inhibition of O-GlcNAcylation of STAT5A on threonine 92 lowers tyrosine phosphorylation of oncogenic STAT5A and ablates malignant transformation. We conclude on strategies for new therapeutic options to block O-GlcNAcylation in combination with tyrosine kinase inhibitors to target neoplastic cancer cell growth and survival.

Original languageEnglish (US)
Article number1028
JournalInternational journal of molecular sciences
Volume20
Issue number5
DOIs
StatePublished - Mar 1 2019

Keywords

  • JAK kinases
  • O-GlcNAc transferase
  • O-GlcNAcase
  • O-GlcNAcylation
  • STAT3
  • STAT5A
  • STAT5B
  • Tyrosine phosphorylation

PubMed: MeSH publication types

  • Journal Article
  • Review

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