PMID- 10196196
OWN - NLM
STAT- MEDLINE
DCOM- 19990517
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 16
DP  - 1999 Apr 16
TI  - SPI-B activates transcription via a unique proline, serine, and threonine domain 
      and exhibits DNA binding affinity differences from PU.1.
PG  - 11115-24
AB  - SPI-B is a B lymphocyte-specific Ets transcription factor that shares a high
      degree of similarity with PU.1/SPI-1. In direct contrast to PU.1(-/-) mice that
      die in utero and lack monocytes, neutrophils, B cells, and T cells, Spi-B-/- mice
      are viable and exhibit a severe B cell proliferation defect. Since PU.1 is
      expressed at wild type levels in Spi-B-/- B cells, the mutant mice provide
      genetic evidence that SPI-B and PU.1 have at least some non-redundant roles in B 
      lymphocytes. To begin to understand the molecular basis for these defects, we
      delineated functional domains of SPI-B for comparison to those of PU.1. By using 
      a heterologous co-transfection system, we identified two independent
      transactivation domains in the N terminus of SPI-B. Interestingly, only one of
      these domains (amino acids 31-61), a proline/serine/threonine-rich region, unique
      among Ets proteins, is necessary for transactivation of the immunoglobulin lambda
      light chain enhancer. This transactivation motif is in marked contrast to PU.1,
      which contains acidic and glutamine-rich domains. In addition, we describe a
      functional PU.1 site within the c-FES promoter which SPI-B fails to bind
      efficiently and transactivate. Finally, we show that SPI-B interacts with the
      PU.1 cofactors Pip, TBP, c-Jun and with lower affinity to nuclear factor
      interleukin-6beta and retinoblastoma. Taken together, these data suggest that
      SPI-B binds DNA with a different affinity for certain sites than PU.1 and harbors
      different transactivation domains. We conclude that SPI-B may activate unique
      target genes in B lymphocytes and interact with unique, although currently
      unidentified, cofactors.
FAU - Rao, S
AU  - Rao S
AD  - Department of Pathology, the University of Chicago, Chicago, Illinois 60637, USA.
FAU - Matsumura, A
AU  - Matsumura A
FAU - Yoon, J
AU  - Yoon J
FAU - Simon, M C
AU  - Simon MC
LA  - eng
GR  - HL5-2094/HL/NHLBI 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 (Amino Acids)
RN  - 0 (DNA Primers)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - 0 (proto-oncogene protein Spi-1)
RN  - 148350-00-9 (SPIB protein, human)
RN  - 2ZD004190S (Threonine)
RN  - 452VLY9402 (Serine)
RN  - 9DLQ4CIU6V (Proline)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (Fes protein, mouse)
RN  - EC 2.7.10.2 (Proto-Oncogene Proteins c-fes)
SB  - IM
MH  - Amino Acid Sequence
MH  - Amino Acids/metabolism
MH  - Animals
MH  - Base Sequence
MH  - DNA Primers
MH  - DNA-Binding Proteins/chemistry/*metabolism
MH  - Enhancer Elements, Genetic
MH  - Mice
MH  - Mutagenesis, Site-Directed
MH  - Proline/*metabolism
MH  - Promoter Regions, Genetic
MH  - *Protein-Tyrosine Kinases
MH  - Proto-Oncogene Proteins/chemistry/genetics/metabolism
MH  - Proto-Oncogene Proteins c-fes
MH  - Serine/*metabolism
MH  - Structure-Activity Relationship
MH  - Threonine/*metabolism
MH  - Trans-Activators/chemistry/metabolism
MH  - Transcription Factors/chemistry/*metabolism
MH  - *Transcriptional Activation
EDAT- 1999/04/10 00:00
MHDA- 1999/04/10 00:01
CRDT- 1999/04/10 00:00
PHST- 1999/04/10 00:00 [pubmed]
PHST- 1999/04/10 00:01 [medline]
PHST- 1999/04/10 00:00 [entrez]
AID - 10.1074/jbc.274.16.11115 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Apr 16;274(16):11115-24. doi: 10.1074/jbc.274.16.11115.