Back to Search
Start Over
SET1A-Mediated Mono-Methylation at K342 Regulates YAP Activation by Blocking Its Nuclear Export and Promotes Tumorigenesis
- Source :
- Cancer Cell. 34:103-118.e9
- Publication Year :
- 2018
- Publisher :
- Elsevier BV, 2018.
-
Abstract
- Summary YAP, a key effector of Hippo pathway, is activated by its translocation from cytoplasm to nucleus to regulate gene expression and promote tumorigenesis. Although the mechanism by which YAP is suppressed in cytoplasm has been well-studied, how the activated YAP is sequestered in the nucleus remains unknown. Here, we demonstrate that YAP is a nucleocytoplasmic shuttling protein and its nuclear export is controlled by SET1A-mediated mono-methylation of YAP at K342, which disrupts the binding of YAP to CRM1. YAP mimetic methylation knockin mice are more susceptible to colorectal tumorigenesis. Clinically, YAP K342 methylation is reversely correlated with cancer survival. Collectively, our study identifies SET1A-mediated mono-methylation at K342 as an essential regulatory mechanism for regulating YAP activity and tumorigenesis.
- Subjects :
- 0301 basic medicine
Cancer Research
Lung Neoplasms
Active Transport, Cell Nucleus
Cell Cycle Proteins
Chromosomal translocation
medicine.disease_cause
Methylation
03 medical and health sciences
Gene expression
medicine
Animals
Humans
Protein Interaction Domains and Motifs
Nuclear export signal
Adaptor Proteins, Signal Transducing
Cell Proliferation
Cell Nucleus
Mice, Knockout
Hippo signaling pathway
Effector
Chemistry
Lysine
YAP-Signaling Proteins
Histone-Lysine N-Methyltransferase
Phosphoproteins
Prognosis
Tumor Burden
Cell biology
Mice, Inbred C57BL
Cell Transformation, Neoplastic
HEK293 Cells
030104 developmental biology
Oncology
A549 Cells
Cytoplasm
Colorectal Neoplasms
Carcinogenesis
Protein Processing, Post-Translational
HeLa Cells
Protein Binding
Signal Transduction
Transcription Factors
Subjects
Details
- ISSN :
- 15356108
- Volume :
- 34
- Database :
- OpenAIRE
- Journal :
- Cancer Cell
- Accession number :
- edsair.doi.dedup.....8076493b3b1d3e4f875c4045c652919c