Hacking RNA: Hakai promotes tumorigenesis by enhancing the RNA-binding function of PSF.
Hakai, an E3 ubiquitin ligase for the E-cadherin complex, plays a crucial role in lowering cell-cell contacts in epithelial cells, a hallmark feature of tumor progression. Recently, Hakai was also found to interact with PSF (PTB-associated splicing factor). While PSF can function as a DNA-binding protein with a tumor suppressive function, its association with Hakai promotes PSF's RNA-binding ability and post-transcriptional influence on target mRNAs. Hakai overexpression enhanced the binding of PSF to mRNAs encoding cancer-related proteins, while knockdown of Hakai reduced the RNA-binding ability of PSF. Furthermore, the knockdown of PSF suppressed Hakai-induced cell proliferation. Thus, Hakai can affect the oncogenic phenotype both by altering E-cadherin-based intercellular adhesions and by increasing PSF's ability to bind RNAs that promote cancer-related gene expression.
Figueroa
Angélica
A
Instituto de Investigación Biomédica A Coruña (INIBIC), Complejo Hospitalario Universitario A Coruña, A Coruña, Spain. conde-valvis@sergas.es
Fujita
Yasuyuki
Y
Gorospe
Myriam
M
D015820:Cadherins / Q000378:metabolism*; D049109:Cell Proliferation; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000235:genetics*; D015513:Oncogene Proteins / Q000378:metabolism / Q000502:physiology*; D000072670:PTB-Associated Splicing Factor; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism / Q000502:physiology*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism / Q000502:physiology*
D015820:Cadherins; D015513:Oncogene Proteins; D000072670:PTB-Associated Splicing Factor; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C471638:CBLL1 protein, human; D044767:Ubiquitin-Protein Ligases