The established and the predicted roles of dynein light chain in the regulation of mitochondrial apoptosis

Cell Cycle. 2018;17(9):1037-1047. doi: 10.1080/15384101.2018.1464851. Epub 2018 Jul 18.

Abstract

The mitochondrial pathway of apoptosis is regulated by the interplay between the members of Bcl-2 family. Within this family, BH3-only proteins are the sensors of apoptotic stimuli and can trigger apoptosis either by inhibiting the anti-apoptotic Bcl-2-family proteins or by directly activating the effectors Bax and Bak. An expanding body of research suggests that a number of non-Bcl-2 proteins can also interact with Bcl-2 proteins and contribute to the decision of cell fate. Dynein light chain (LC8, DYNLL or DLC), a hub protein and a dimerizing engine has been proposed to regulate the pro-apoptotic activity of two BH3-only proteins, Bim and Bmf. Our recent work has provided insight into the mechanisms through which DLC1 (DYNLL1) modulates Bim activity. Here we discuss the present day understanding of Bim-DLC interaction and endeavor to evaluate this interaction in the light of information from studies of DLC with other binding partners.

Keywords: Apoptosis; Bim; Bmf; dynein light chain (DLC); intrinsically disordered protein; nanny protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Apoptosis / physiology*
  • Bcl-2-Like Protein 11 / metabolism
  • Cell Membrane Permeability / physiology
  • Dyneins / classification
  • Dyneins / metabolism*
  • Humans
  • Intrinsically Disordered Proteins / metabolism
  • Mitochondria / metabolism*
  • Mitochondrial Membrane Transport Proteins / metabolism
  • Myeloid Cell Leukemia Sequence 1 Protein / metabolism
  • Phosphorylation
  • Protein Binding
  • bcl-2 Homologous Antagonist-Killer Protein / metabolism
  • bcl-2-Associated X Protein / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • BAK1 protein, human
  • BMF protein, human
  • Bcl-2-Like Protein 11
  • Intrinsically Disordered Proteins
  • MCL1 protein, human
  • Mitochondrial Membrane Transport Proteins
  • Myeloid Cell Leukemia Sequence 1 Protein
  • RTL10 protein, human
  • bcl-2 Homologous Antagonist-Killer Protein
  • bcl-2-Associated X Protein
  • Dyneins

Grants and funding

This work was supported by the Deutsche Forschungsgemeinschaft [DFG-FOR-2036].