PMID- 10347144
OWN - NLM
STAT- MEDLINE
DCOM- 19990701
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 23
DP  - 1999 Jun 4
TI  - Identification and characterization of a novel cytokine, THANK, a TNF homologue
      that activates apoptosis, nuclear factor-kappaB, and c-Jun NH2-terminal kinase.
PG  - 15978-81
AB  - By using the amino acid sequence motif of tumor necrosis factor (TNF), we
      searched the expressed sequence tag data base and identified a novel full-length 
      cDNA encoding 285 amino acid residues and named it THANK. THANK is a type II
      transmembrane protein with 15-20% overall amino acid sequence homology to TNF,
      LT-alpha, FasL, and LIGHT, all members of the TNF family. The mRNA for THANK was 
      expressed at high levels by peripheral blood leukocytes, lymph node, spleen, and 
      thymus and at low levels by small intestine, pancreas, placenta, and lungs. THANK
      was also prominently expressed in hematopoietic cell lines. The recombinant
      purified protein expressed in the baculovirus system had an approximate molecular
      size 20 kDa with amino-terminal sequence of AVQGP. Treatment of human myeloid
      U937 cells with purified THANK activated nuclear transcription factor-kappaB
      (NF-kappaB) consisting of p50 and p65. Activation was time- and dose-dependent,
      beginning with as little as a 1 pM amount of the cytokines and as early as 15
      min. Under the same conditions, THANK also activated c-jun NH2-terminal kinase
      (JNK) in U937 cells. THANK also strongly suppressed the growth of tumor cell
      lines and activated caspase-3. Although THANK had all the activities and potency 
      of TNF, it did not bind to the TNF receptors. Thus our results indicate that
      THANK is a novel cytokine that belongs to the TNF family and activates apoptosis,
      NF-kappaB, and JNK through a distinct receptor.
FAU - Mukhopadhyay, A
AU  - Mukhopadhyay A
AD  - Cytokine Research Laboratory, Department of Molecular Oncology, The University of
      Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
FAU - Ni, J
AU  - Ni J
FAU - Zhai, Y
AU  - Zhai Y
FAU - Yu, G L
AU  - Yu GL
FAU - Aggarwal, B B
AU  - Aggarwal BB
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (B-Cell Activating Factor)
RN  - 0 (Cytokines)
RN  - 0 (Membrane Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (Recombinant Proteins)
RN  - 0 (TNFSF13B protein, human)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 3.4.22.- (CASP3 protein, human)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - *Apoptosis
MH  - B-Cell Activating Factor
MH  - Binding Sites
MH  - Calcium-Calmodulin-Dependent Protein Kinases/*metabolism
MH  - Caspase 3
MH  - Caspases/metabolism
MH  - Cell Division/drug effects
MH  - Cloning, Molecular
MH  - Cytokines/*chemistry/*isolation & purification/metabolism
MH  - Databases, Factual
MH  - Enzyme Activation
MH  - Humans
MH  - JNK Mitogen-Activated Protein Kinases
MH  - Membrane Proteins/*chemistry/*isolation & purification/metabolism
MH  - *Mitogen-Activated Protein Kinases
MH  - Molecular Sequence Data
MH  - NF-kappa B/*metabolism
MH  - Rabbits
MH  - Recombinant Proteins/metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - U937 Cells
EDAT- 1999/05/29 00:00
MHDA- 1999/05/29 00:01
CRDT- 1999/05/29 00:00
PHST- 1999/05/29 00:00 [pubmed]
PHST- 1999/05/29 00:01 [medline]
PHST- 1999/05/29 00:00 [entrez]
AID - 10.1074/jbc.274.23.15978 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Jun 4;274(23):15978-81. doi: 10.1074/jbc.274.23.15978.