PMID- 12324461
OWN - NLM
STAT- MEDLINE
DCOM- 20030204
LR  - 20231213
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 277
IP  - 49
DP  - 2002 Dec 6
TI  - Molecular basis for the loss of CD28 expression in senescent T cells.
PG  - 46940-9
AB  - CD28(null) T cells are the most consistent biological indicator of the aging 
      immune system in humans and are predictors of immunoincompetence in the elderly. 
      The loss of CD28 is the result of an inoperative transcriptional initiator (INR), 
      which consists of two nonoverlapping alpha and beta motifs that have distinct 
      protein binding profiles but function as a unit. In CD28(null) T cells, there is 
      a coordinate loss of alpha-/beta-bound complexes, hence the alphabeta-INR is 
      inactive. In the present work therefore, studies were conducted to identify the 
      components of such complexes that may account for the trans-activation of the 
      alphabeta-INR. By affinity chromatography and tandem mass spectrometry, two 
      proteins, namely, nucleolin and the A isoform of heterogeneous nuclear 
      ribonucleoprotein-D0 (hnRNP-D0A), were identified to be among the key components 
      of the site alpha complex. In DNA binding assays, specific antibodies indicated 
      their antigenic presence in alpha-bound complexes. Transcription assays showed 
      that they are both required in the trans-activation of alphabeta-INR-driven DNA 
      templates. Because CD28 is T cell-restricted, and nucleolin and hnRNP-D0A are 
      ubiquitous proteins, these results support the notion that cell-specific 
      functions can be regulated by commonly expressed proteins. The present data also 
      provide evidence for INR-regulated transcription that is independent of the known 
      components of the basal transcription complex.
FAU - Vallejo, Abbe N
AU  - Vallejo AN
AD  - Department of Medicine and Immunology, Mayo Clinic, Rochester, Minnesota 55905, 
      USA. vallejo.abbe@mayo.edu
FAU - Bryl, Ewa
AU  - Bryl E
FAU - Klarskov, Klaus
AU  - Klarskov K
FAU - Naylor, Stephen
AU  - Naylor S
FAU - Weyand, Cornelia M
AU  - Weyand CM
FAU - Goronzy, Jorg J
AU  - Goronzy JJ
LA  - eng
GR  - R03 AR045830-03/AR/NIAMS NIH HHS/United States
GR  - R03-AR45830/AR/NIAMS NIH HHS/United States
GR  - R01-AG15043/AG/NIA NIH HHS/United States
GR  - R01-AR41974/AR/NIAMS 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.
DEP - 20020924
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (CD28 Antigens)
RN  - 0 (HNRNPD protein, human)
RN  - 0 (Heterogeneous Nuclear Ribonucleoprotein D0)
RN  - 0 (Heterogeneous-Nuclear Ribonucleoprotein D)
RN  - 0 (Phosphoproteins)
RN  - 0 (Protein Isoforms)
RN  - 0 (RNA-Binding Proteins)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Base Sequence
MH  - Binding Sites
MH  - Blotting, Western
MH  - CD28 Antigens/*biosynthesis/*chemistry
MH  - Cell Nucleus/metabolism
MH  - Cellular Senescence
MH  - Chromatography
MH  - DNA/metabolism
MH  - Exons
MH  - Heterogeneous Nuclear Ribonucleoprotein D0
MH  - Heterogeneous-Nuclear Ribonucleoprotein D/chemistry
MH  - Humans
MH  - Jurkat Cells
MH  - Mass Spectrometry
MH  - Molecular Sequence Data
MH  - Phosphoproteins/chemistry
MH  - Protein Binding
MH  - Protein Isoforms
MH  - RNA-Binding Proteins/chemistry
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Sequence Homology, Nucleic Acid
MH  - Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
MH  - T-Lymphocytes/immunology/*metabolism
MH  - Transcription, Genetic
MH  - Transcriptional Activation
MH  - Nucleolin
EDAT- 2002/09/27 06:00
MHDA- 2003/02/05 04:00
CRDT- 2002/09/27 06:00
PHST- 2002/09/27 06:00 [pubmed]
PHST- 2003/02/05 04:00 [medline]
PHST- 2002/09/27 06:00 [entrez]
AID - S0021-9258(19)71413-6 [pii]
AID - 10.1074/jbc.M207352200 [doi]
PST - ppublish
SO  - J Biol Chem. 2002 Dec 6;277(49):46940-9. doi: 10.1074/jbc.M207352200. Epub 2002 
      Sep 24.