PMID- 10499802
OWN - NLM
STAT- MEDLINE
DCOM- 19991015
LR  - 20190705
IS  - 0092-8674 (Print)
IS  - 0092-8674 (Linking)
VI  - 98
IP  - 6
DP  - 1999 Sep 17
TI  - Cdk phosphorylation triggers sequential intramolecular interactions that
      progressively block Rb functions as cells move through G1.
PG  - 859-69
AB  - We present evidence that phosphorylation of the C-terminal region of Rb by Cdk4/6
      initiates successive intramolecular interactions between the C-terminal region
      and the central pocket. The initial interaction displaces histone deacetylase
      from the pocket, blocking active transcriptional repression by Rb. This
      facilitates a second interaction that leads to phosphorylation of the pocket by
      Cdk2 and disruption of pocket structure. These intramolecular interactions
      provide a molecular basis for sequential phosphorylation of Rb by Cdk4/6 and
      Cdk2. Cdk4/6 is activated early in G1, blocking active repression by Rb. However,
      it is not until near the end of G1, when cyclin E is expressed and Cdk2 is
      activated, that Rb is prevented from binding and inactivating E2F.
FAU - Harbour, J W
AU  - Harbour JW
AD  - Department of Ophthalmology and Visual Sciences, Washington University School of 
      Medicine, St. Louis, Missouri 63110, USA.
FAU - Luo, R X
AU  - Luo RX
FAU - Dei Santi, A
AU  - Dei Santi A
FAU - Postigo, A A
AU  - Postigo AA
FAU - Dean, D C
AU  - Dean DC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Cell
JT  - Cell
JID - 0413066
RN  - 0 (Carrier Proteins)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Cyclin E)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (E2F Transcription Factors)
RN  - 0 (Peptide Fragments)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Retinoblastoma Protein)
RN  - 0 (Retinoblastoma-Binding Protein 1)
RN  - 0 (Transcription Factor DP1)
RN  - 0 (Transcription Factors)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - EC 2.7.11.22 (CDC2-CDC28 Kinases)
RN  - EC 2.7.11.22 (CDK2 protein, human)
RN  - EC 2.7.11.22 (CDK4 protein, human)
RN  - EC 2.7.11.22 (CDK6 protein, human)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinase 2)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinase 4)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinase 6)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinases)
RN  - EC 3.5.1.98 (Histone Deacetylases)
RN  - K3Z4F929H6 (Lysine)
SB  - IM
MH  - *CDC2-CDC28 Kinases
MH  - *Carrier Proteins
MH  - *Cell Cycle Proteins
MH  - Cyclin E/metabolism
MH  - Cyclin-Dependent Kinase 2
MH  - Cyclin-Dependent Kinase 4
MH  - Cyclin-Dependent Kinase 6
MH  - Cyclin-Dependent Kinases/*metabolism
MH  - *DNA-Binding Proteins
MH  - E2F Transcription Factors
MH  - Female
MH  - G1 Phase/*physiology
MH  - *Gene Expression Regulation
MH  - Histone Deacetylases/metabolism
MH  - Humans
MH  - Lysine
MH  - Mutation
MH  - Peptide Fragments/genetics/*metabolism
MH  - Phosphorylation
MH  - Protein Binding
MH  - Protein Conformation
MH  - Protein-Serine-Threonine Kinases/metabolism
MH  - *Proto-Oncogene Proteins
MH  - Retinoblastoma Protein/genetics/*metabolism
MH  - Retinoblastoma-Binding Protein 1
MH  - Transcription Factor DP1
MH  - Transcription Factors/metabolism
MH  - Transcription, Genetic
MH  - Tumor Cells, Cultured
EDAT- 1999/09/28 00:00
MHDA- 1999/09/28 00:01
CRDT- 1999/09/28 00:00
PHST- 1999/09/28 00:00 [pubmed]
PHST- 1999/09/28 00:01 [medline]
PHST- 1999/09/28 00:00 [entrez]
AID - S0092-8674(00)81519-6 [pii]
AID - 10.1016/s0092-8674(00)81519-6 [doi]
PST - ppublish
SO  - Cell. 1999 Sep 17;98(6):859-69. doi: 10.1016/s0092-8674(00)81519-6.