LASS5 Interacts with SDHB and Synergistically Represses p53 and p21 Activity

Curr Mol Med. 2016;16(6):582-90. doi: 10.2174/1566524016666160607090012.


Longevity Assurance 5 (LASS5), a member of the LASS/Ceramide Synthases family, synthesizes C16-ceramide and is implicated in tumor biology. However, its precise role is not yet well understood. A yeast two-hybrid screen was performed using a human cDNA library to identify potential LASS5- interaction partners. One identified clone encodes succinate dehydrogenase subunit B (SDHB). Mammalian two-hybrid assays showed that LASS5 interacts with SDHB, and the result was also confirmed by GST pull-down and coimmunoprecipitation assays. The C-terminal fragment of SDHB was required for the interaction. LASS5 and SDHB were co-localized in COS-7 cells. LASS5 and SDHB expressions were found to be up-regulated in neuroglioma tissue. Transfection assays showed that LASS5 or SDHB expression repressed p53 or p21 reporter activity, respectively. Simultaneous LASS5 and SDHB expression resulted in stronger repression of p53 and p21 reporter activity, suggesting that LASS5 and SDHB interaction may synergistically affect transcriptional regulation of p53 and p21. Our data provide new molecular insights into potential roles of LASS5 and SDHB in tumor biology.

MeSH terms

  • Animals
  • COS Cells
  • Cell Line, Tumor
  • Ceramides
  • Chlorocebus aethiops
  • Cloning, Molecular
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics*
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Gene Expression
  • Gene Expression Regulation, Neoplastic*
  • Gene Library
  • HeLa Cells
  • Humans
  • Mutation
  • Neuroglia / metabolism
  • Neuroglia / pathology
  • Protein Binding
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Signal Transduction
  • Sphingosine N-Acyltransferase
  • Succinate Dehydrogenase / genetics*
  • Succinate Dehydrogenase / metabolism
  • Transcription, Genetic
  • Tumor Suppressor Protein p53 / genetics*
  • Tumor Suppressor Protein p53 / metabolism


  • Ceramides
  • Cyclin-Dependent Kinase Inhibitor p21
  • Recombinant Proteins
  • Tumor Suppressor Protein p53
  • N-palmitoylsphingosine
  • SDHB protein, human
  • Succinate Dehydrogenase
  • CERS5 protein, human
  • Sphingosine N-Acyltransferase