TNFalpha disrupts mitotic clonal expansion and regulation of retinoblastoma proteins p130 and p107 during 3T3-L1 adipocyte differentiation.
The inhibitory effects of TNFalpha on adipocyte differentiation are well described, however, the mechanisms are poorly understood. Early during hormonally-induced 3T3-L1 preadipocyte differentiation there is a requisite mitotic clonal expansion phase that is associated with significant regulation in p130 and p107 protein levels, two members of the retinoblastoma protein family that regulate cell cycle events through interactions with the E2F transcription factors. This regulation occurs within the first 24 hours of differentiation (Day 1) and is characterized by a transient increase in p107 protein and mRNA levels as well as a transient decrease in p130 protein levels. Here we describe that TNFalpha disrupts the normal pattern of expression of both p130 and p107 proteins, leading to a complete block in mitotic clonal expansion. Interestingly, TNFalpha-treated cells enter S-phase as determined by 5-bromo-2'-deoxyuridine uptake experiments, but rather than completing cell cycle, they are stimulated to undergo apoptosis.
Lyle
R E
RE
Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, 72205, USA.
Richon
V M
VM
McGehee
R E
RE
D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D007150:Immunohistochemistry; D051379:Mice; D008970:Molecular Weight; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011506:Proteins; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D050720:Retinoblastoma-Like Protein p107; D050717:Retinoblastoma-Like Protein p130; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D009687:Nuclear Proteins; D010750:Phosphoproteins; D011506:Proteins; D012333:RNA, Messenger; C489485:Rbl1 protein, mouse; C493838:Rbl2 protein, mouse; D016160:Retinoblastoma Protein; D050720:Retinoblastoma-Like Protein p107; D050717:Retinoblastoma-Like Protein p130; D014409:Tumor Necrosis Factor-alpha