Human cytomegalovirus-encoded viral cyclin-dependent kinase (v-CDK) UL97 phosphorylates and inactivates the retinoblastoma protein-related p107 and p130 proteins

Satoko Iwahori, Angie C. Umaña, Halena R. VanDeusen, Robert F. Kalejta

研究成果: Article査読

18 被引用数 (Scopus)

抄録

The human cytomegalovirus (HCMV)-encoded viral cyclindependent kinase (v-CDK) UL97 phosphorylates the retinoblastoma (Rb) tumor suppressor. Here, we identify the other Rb family members p107 and p130 as novel targets of UL97. UL97 phosphorylates p107 and p130 thereby inhibiting their ability to represstheE2F-responsiveE2F1promoter.AswithRb,thisphosphorylation, and the rescue of E2F-responsive transcription, is dependent on the L1 LXCXE motif in UL97 and its interacting clefts on p107 and p130. Interestingly, UL97 does not induce the disruption of all p107-E2F or p130-E2F complexes, as it does to Rb-E2F complexes. UL97 strongly interacts with p107 but not Rb or p130. Thus the inhibitory mechanisms of UL97 for Rb family protein-mediated repression of E2F-responsive transcription appear to differ for each of the Rb family proteins. The immediate early 1 (IE1) protein ofHCMValso rescues p107-and p130-mediated repression of E2F-responsive gene expression, but it does not induce their phosphorylation and does not disrupt p107-E2F or p130-E2F complexes. The unique regulation of Rb family proteins byHCMVUL97 and IE1 attests to the importance of modulating Rb family protein function in HCMV-infected cells.

本文言語English
ページ(範囲)6583-6599
ページ数17
ジャーナルJournal of Biological Chemistry
292
16
DOI
出版ステータスPublished - 21-04-2017
外部発表はい

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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