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Developmentally regulated alternative splicing of anti‐apoptotic proteins during adipogenesis
Author(s) -
Patel Niketa A.,
Apostolatos Andre,
Yoder Sean,
Ghansah Tomar,
Watson James E.,
Cooper Denise R.,
Li Pengfei
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.900.5
Subject(s) - adipogenesis , alternative splicing , microbiology and biotechnology , apoptosis , biology , rna splicing , protein kinase c , signal transduction , messenger rna , gene , genetics , rna , mesenchymal stem cell
Novel therapies to treat obesity and insulin resistance will benefit millions of people. 3T3‐L1 cell differentiation provides a model parallel to mouse adipogenesis. Pre‐adipocytes undergo apoptosis while mature adipocytes don't undergo apoptosis. The basis for this is poorly understood. Analysis of the differentiation of pre‐adipocytes using RT‐PCR, Western analysis and microarrays from days (D) 0 to 10 showed substantial changes in the expression of alternatively spliced proteins involved in apoptosis: PKCδ, caspase‐9 and Bcl‐x, suggesting post‐transcriptional control of adipogenesis. PKCδ is a crucial signaling kinase affecting downstream apoptotic pathways. On D0, cells expressed the apoptotic splice variants PKCδI, caspase 9a and Bcl‐xS. By D6, cells started expressing the anti‐apoptotic proteins PKCδII, caspase 9b and Bcl‐xL with a concurrent decrease in pro‐apoptotic proteins. Expression of PKCβII, pBAD, pPTEN, pAKT and Bcl2 involved in proliferation and survival, also increased by D6. We observed that the switch in splice variants was accompanied by increased expression of SR splicing factors which modulate alternative splicing. Hence, the programmed splicing of anti‐apoptotic proteins is a pivotal switch in differentiation that commits cells to a pro‐survival pathway. It may be possible to modulate adipogenesis for therapeutic treatments of obesity. Supported by NIDDK 054393 and VA.