TY - JOUR
T1 - Human cytomegalovirus-encoded viral cyclin-dependent kinase (v-CDK) UL97 phosphorylates and inactivates the retinoblastoma protein-related p107 and p130 proteins
AU - Iwahori, Satoko
AU - Umaña, Angie C.
AU - VanDeusen, Halena R.
AU - Kalejta, Robert F.
N1 - Funding Information:
This work was supported in part by National Institutes of Health Grants R01-AI080675 (to R. F. K.) and P01-CA022443
Publisher Copyright:
© 2017 by The American Society for Biochemistry and Molecular Biology, Inc.
PY - 2017/4/21
Y1 - 2017/4/21
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.M116.773150
DO - 10.1074/jbc.M116.773150
M3 - Article
C2 - 28289097
AN - SCOPUS:85018569994
VL - 292
SP - 6583
EP - 6599
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 16
ER -