PMID- 16985255
OWN - NLM
STAT- MEDLINE
DCOM- 20070319
LR  - 20131121
IS  - 0193-1849 (Print)
IS  - 0193-1849 (Linking)
VI  - 292
IP  - 2
DP  - 2007 Feb
TI  - Degradation of STAT5 proteins in 3T3-L1 adipocytes is induced by TNF-alpha and 
      cycloheximide in a manner independent of STAT5A activation.
PG  - E461-8
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a multifunctional cytokine that has 
      been implicated as a causative factor in obesity-linked insulin resistance. It is 
      commonly accepted that macrophage-derived TNF-alpha acts in a paracrine manner on 
      adjacent adipocytes to inhibit the expression of various adipocyte genes and to 
      attenuate insulin signaling. Several studies have revealed that signal transducer 
      and activator of transcription (STAT)5 proteins are modulated during adipogenesis 
      and can modulate the transcription of some adipocyte genes. In this study, we 
      demonstrate that TNF-alpha treatment, in the presence of cycloheximide, also 
      results in the rapid turnover of STAT5A and STAT5B in a process that is 
      independent of STAT5 activation by tyrosine phosphorylation. In addition, STAT5B 
      is more labile than STAT5A under these conditions, suggesting that the COOH 
      terminus of STAT5 may be involved in the turnover of each protein. Initial 
      characterization of the TNF-alpha and cycloheximide-mediated degradation of STAT5 
      indicates that inhibition of the proteasome stabilizes both forms of STAT5 in the 
      presence of TNF-alpha. In addition, the use of an NF-kappaB inhibitor results in 
      the stabilization of STAT5A in the presence of TNF-alpha and cycloheximide, 
      indicating that the degradation of STAT5 proteins under these conditions may 
      involve the NF-kappaB pathway. STAT5 proteins are abundantly expressed in mature 
      adipocytes and are normally extremely stable proteins under a wide range of 
      conditions. However, our results demonstrate that the potentiation of 
      TNF-alpha-mediated signaling in the presence of cyclohexmide is associated with a 
      significant increase in the degradation of STAT5 proteins in 3T3-L1 adipocytes.
FAU - Floyd, Z Elizabeth
AU  - Floyd ZE
AD  - Department of Biological Sciences, Louisiana State University, 202 Life Sciences 
      Bldg., Baton Rouge, LA 70803, USA.
FAU - Segura, Brant M
AU  - Segura BM
FAU - He, Fang
AU  - He F
FAU - Stephens, Jacqueline M
AU  - Stephens JM
LA  - eng
GR  - R01-DK-52968-05/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20060919
PL  - United States
TA  - Am J Physiol Endocrinol Metab
JT  - American journal of physiology. Endocrinology and metabolism
JID - 100901226
RN  - 0 (NF-kappa B)
RN  - 0 (STAT5 Transcription Factor)
RN  - 0 (Stat5a protein, mouse)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 9002-72-6 (Growth Hormone)
RN  - 98600C0908 (Cycloheximide)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
SB  - IM
MH  - 3T3-L1 Cells
MH  - Adipocytes/*drug effects/metabolism
MH  - Animals
MH  - Cycloheximide/*pharmacology
MH  - Growth Hormone/pharmacology
MH  - MAP Kinase Signaling System/physiology
MH  - Mice
MH  - NF-kappa B/metabolism/physiology
MH  - Phosphatidylinositol 3-Kinases/physiology
MH  - Proteasome Endopeptidase Complex/metabolism/physiology
MH  - Protein Denaturation/drug effects
MH  - STAT5 Transcription Factor/*metabolism
MH  - Tumor Necrosis Factor-alpha/*pharmacology
EDAT- 2006/09/21 09:00
MHDA- 2007/03/21 09:00
CRDT- 2006/09/21 09:00
PHST- 2006/09/21 09:00 [pubmed]
PHST- 2007/03/21 09:00 [medline]
PHST- 2006/09/21 09:00 [entrez]
AID - 00334.2006 [pii]
AID - 10.1152/ajpendo.00334.2006 [doi]
PST - ppublish
SO  - Am J Physiol Endocrinol Metab. 2007 Feb;292(2):E461-8. doi: 
      10.1152/ajpendo.00334.2006. Epub 2006 Sep 19.