Nucleo-cytoplasmic shuttling of 14-3-3 epsilon carrying hnRNP C promotes autophagy

Cancer Biol Ther. 2023 Dec 31;24(1):2246203. doi: 10.1080/15384047.2023.2246203.

Abstract

Translocation of 14-3-3 protein epsilon (14-3-3ε) was found to be involved in Triptolide (Tp)-induced inhibition of colorectal cancer (CRC) cell proliferation. However, the form of cell death induced by 14-3-3ε translocation and mechanisms underlying this effect remain unclear. This study employed label-free LC-MS/MS to identify 14-3-3ε-associated proteins in CRC cells treated with or without Tp. Our results confirmed that heterogeneous nuclear ribonucleoproteins C1/C2 (hnRNP C) were exported out of the nucleus by 14-3-3ε and degraded by ubiquitination. The nucleo-cytoplasmic shuttling of 14-3-3ε carrying hnRNP C mediated Tp-induced proliferation inhibition, cell cycle arrest and autophagic processes. These findings have broad implications for our understanding of 14-3-3ε function, provide an explanation for the mechanism of nucleo-cytoplasmic shuttling of hnRNP C and provide new insights into the complex regulation of autophagy.

Keywords: 14-3-3ε; Triptolide; autophagy; hnRNP C; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 14-3-3 Proteins* / metabolism
  • Autophagy*
  • Chromatography, Liquid
  • Cytoplasm
  • Heterogeneous-Nuclear Ribonucleoprotein Group C* / metabolism
  • Heterogeneous-Nuclear Ribonucleoproteins
  • Humans
  • Tandem Mass Spectrometry

Substances

  • Heterogeneous-Nuclear Ribonucleoproteins
  • triptolide
  • YWHAE protein, human
  • 14-3-3 Proteins
  • Heterogeneous-Nuclear Ribonucleoprotein Group C
  • HNRNPC protein, human

Grants and funding

The work was supported by the Guizhou Education Department Youth Science and Technology Talents Growth Project [KY[2018]173]; National Natural Science Foundation of China [81472315]; Natural Science Foundation of Guangdong Province [2022A1515012552].