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Increased expression of Drosophila tetraspanin, Tsp68C, suppresses the abnormal proliferation of ytr-deficient and Ras/Raf-activated hemocytes.

Publication ,  Journal Article
Sinenko, SA; Mathey-Prevot, B
Published in: Oncogene
December 2, 2004

Tetraspanins are evolutionary conserved transmembrane proteins thought to facilitate cell proliferation, movement or fusion by acting as organizers of different signaling events. Despite their prevalence and conservation, their specific role and functions remain largely elusive, as their redundancy in various organisms has hindered loss of function studies. Here, we take a gain of function approach to study Drosophila tetraspanin Tsp68C and its effect on larval hemocytes. We recently characterized a lethal mutation in ytr, a conserved gene that encodes a nuclear arginine-rich protein of unknown function, which is accompanied by abnormal differentiation and proliferation of the larval hematopoietic tissue in flies. A hemolectin (hml)-Gal4 construct carried by hml-Gal4 transgenic flies was sufficient by itself to abrogate the hematopoietic defects in ytr mutant larvae. This rescue correlated with the overexpression of tsp68C, a tetraspanin gene nested in the hml promoter. The suppression of abnormal proliferation by the hml-Gal4 construct was not restricted to ytr-deficient hemocytes, but was also observed in hemocytes expressing the oncogenic forms of Raf or Ras proteins. However, it had no effect on overproliferation mediated by a constitutively active form of Jak. New hml-Gal4 lines, in which the tsp68C gene was silenced or deleted from the promoter, no longer rescued the hematopoietic defect in ytr mutants nor suppressed the activated Raf-induced overproliferation. Therefore, change in tetraspanin Tsp68C expression has a strong suppressor effect on abnormal proliferation and differentiation of hemocytes in the context of specific lesions, such as overactivation of the Ras/Raf/MAPK pathway.

Duke Scholars

Published In

Oncogene

DOI

ISSN

0950-9232

Publication Date

December 2, 2004

Volume

23

Issue

56

Start / End Page

9120 / 9128

Location

England

Related Subject Headings

  • raf Kinases
  • Sequence Homology, Amino Acid
  • Reverse Transcriptase Polymerase Chain Reaction
  • Proto-Oncogene Proteins p21(ras)
  • Promoter Regions, Genetic
  • Oncology & Carcinogenesis
  • Nuclear Proteins
  • Mutation
  • Molecular Sequence Data
  • Membrane Proteins
 

Citation

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Sinenko, S. A., & Mathey-Prevot, B. (2004). Increased expression of Drosophila tetraspanin, Tsp68C, suppresses the abnormal proliferation of ytr-deficient and Ras/Raf-activated hemocytes. Oncogene, 23(56), 9120–9128. https://doi.org/10.1038/sj.onc.1208156
Sinenko, Sergey A., and Bernard Mathey-Prevot. “Increased expression of Drosophila tetraspanin, Tsp68C, suppresses the abnormal proliferation of ytr-deficient and Ras/Raf-activated hemocytes.Oncogene 23, no. 56 (December 2, 2004): 9120–28. https://doi.org/10.1038/sj.onc.1208156.
Sinenko, Sergey A., and Bernard Mathey-Prevot. “Increased expression of Drosophila tetraspanin, Tsp68C, suppresses the abnormal proliferation of ytr-deficient and Ras/Raf-activated hemocytes.Oncogene, vol. 23, no. 56, Dec. 2004, pp. 9120–28. Pubmed, doi:10.1038/sj.onc.1208156.

Published In

Oncogene

DOI

ISSN

0950-9232

Publication Date

December 2, 2004

Volume

23

Issue

56

Start / End Page

9120 / 9128

Location

England

Related Subject Headings

  • raf Kinases
  • Sequence Homology, Amino Acid
  • Reverse Transcriptase Polymerase Chain Reaction
  • Proto-Oncogene Proteins p21(ras)
  • Promoter Regions, Genetic
  • Oncology & Carcinogenesis
  • Nuclear Proteins
  • Mutation
  • Molecular Sequence Data
  • Membrane Proteins