PMID- 10593981
OWN - NLM
STAT- MEDLINE
DCOM- 20000127
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 51
DP  - 1999 Dec 17
TI  - Phosphorylation of B-Myb regulates its transactivation potential and DNA binding.
PG  - 36741-9
AB  - The transcription factor B-Myb is a cell cycle-regulated phosphoprotein and a
      potent regulator of cell cycle progression. Previous studies demonstrated that
      B-Myb was phosphorylated at the onset of S phase, suggesting that it could be due
      to cyclin-dependent kinases. We identified 10 B-Myb phosphorylation sites by
      automated peptide radiosequencing of tryptic phosphopeptides derived from in vivo
      (32)P-labeled B-Myb. Each B-Myb phosphorylation site contained a phosphoserine or
      phosphothreonine followed by a proline, suggesting that this phosphorylation is
      due to a proline-directed kinase. Cyclin A-Cdk2 and cyclin E-Cdk2 complexes each 
      phosphorylated B-Myb in a cell-free system on the same sites as in intact cells. 
      Furthermore, the ability of B-Myb to activate a reporter plasmid was enhanced by 
      the cotransfection of cyclin A, whereas mutagenesis of the 10 identified
      phosphorylation sites from B-Myb blocked the effect of cyclin A coexpression.
      Additional analysis revealed that the effect of phosphorylation on B-Myb
      transactivation potential was enhanced by phosphorylation sites in its
      carboxyl-terminal half. One phosphorylation site (Ser(581)) appeared to
      negatively regulate DNA binding, as mutation of this site enhanced the ability of
      B-Myb to bind a Myb-binding sequence. These data suggest that B-Myb is a target
      for phosphorylation by cyclin-Cdk2 and that phosphorylation of B-Myb regulates
      its transcriptional activity.
FAU - Johnson, T K
AU  - Johnson TK
AD  - Eppley Institute for Research in Cancer and Allied Diseases, University of
      Nebraska Medical Center, Omaha, Nebraska 68198-6805, USA.
FAU - Schweppe, R E
AU  - Schweppe RE
FAU - Septer, J
AU  - Septer J
FAU - Lewis, R E
AU  - Lewis RE
LA  - eng
GR  - CA09476/CA/NCI NIH HHS/United States
GR  - P30 CA36727/CA/NCI NIH HHS/United States
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  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Oncogene Proteins)
RN  - 0 (Trans-Activators)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - *Cell Cycle Proteins
MH  - Cell Line
MH  - Cell-Free System
MH  - DNA/*metabolism
MH  - DNA-Binding Proteins/*genetics/*metabolism
MH  - Molecular Sequence Data
MH  - Oncogene Proteins/genetics/metabolism
MH  - Phosphorylation
MH  - Protein Binding
MH  - Trans-Activators/*genetics/*metabolism
MH  - *Transcriptional Activation
MH  - Transfection
EDAT- 1999/12/14 00:00
MHDA- 1999/12/14 00:01
CRDT- 1999/12/14 00:00
PHST- 1999/12/14 00:00 [pubmed]
PHST- 1999/12/14 00:01 [medline]
PHST- 1999/12/14 00:00 [entrez]
AID - 10.1074/jbc.274.51.36741 [doi]
AID - S0021-9258(19)53225-2 [pii]
PST - ppublish
SO  - J Biol Chem. 1999 Dec 17;274(51):36741-9. doi: 10.1074/jbc.274.51.36741.