Inactivation of retinoblastoma protein in uveal melanoma by phosphorylation of sites in the COOH-terminal region

Jr Brantley M.A., J. William Harbour

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

Uveal melanoma is the most common malignancy of the eye, but little is known about its underlying genetic defects. Melanomas of uveal origin, unlike those of the skin, are rarely familial and have not been linked consistently to mutations in tumor suppressor genes. Here, we investigated the Rb pathway in uveal melanoma. Most tumors displayed strong immunostaining for Rb and p16, suggesting that they were not mutationally inactivated. However, Rb was frequently phosphorylated at serine-807 and serine-811, and cyclin D1 was expressed in many of the tumors. Mutation of these serine residues prevented cyclin D-dependent phosphorylation from inactivating Rb in cultured cells. We conclude that Rb is frequently inactivated in uveal melanoma by phosphorylation of residues in the COOH-terminal region that regulate its activity, and one mechanism for this phosphorylation is overexpression of cyclin D.

Original languageEnglish
Pages (from-to)4320-4323
Number of pages4
JournalCancer Research
Volume60
Issue number16
StatePublished - Aug 15 2000
Externally publishedYes

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Retinoblastoma Protein
Phosphorylation
Serine
Cyclin D
Neoplasms
Mutation
Cyclin D1
Tumor Suppressor Genes
Cultured Cells
Skin
Uveal melanoma

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Inactivation of retinoblastoma protein in uveal melanoma by phosphorylation of sites in the COOH-terminal region. / Brantley M.A., Jr; William Harbour, J.

In: Cancer Research, Vol. 60, No. 16, 15.08.2000, p. 4320-4323.

Research output: Contribution to journalArticle

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