STAT5A (signal transducer and activator of transcription 5A) is a transcription factor that plays a role in adipocyte development and function. Although the role of STAT5A in fat cell development is well characterized, its specific roles in mature fat cells are still largely unknown. Moreover, the potential role of STAT5A in metabolic diseases, in particular type 2 diabetes, remains unclear. To further understand the function of STAT5A in adipocytes, we employed a non-biased co-immunoprecipitation and mass-spectrometry-based approach to identify novel STAT5A-interacting proteins. One of the proteins we identified was DBC1 (deleted in breast cancer 1; also known as CCAR2). DBC1 is typically localized in the nucleus and has been primarily studied in tumor cells. However, the functions of DBC1 in adipocytes are relatively unknown. Using mouse fat cells, we confirmed that there is a physical association between endogenous STAT5A and DBC1 proteins under physiological conditions in the nucleus that is not dependent upon STAT5 tyrosine phosphorylation. Knockdown of DBC1 in 3T3-L1 adipocytes using siRNA did not affect the expression of several STAT5A target genes including socs3, cish, bcl-6, socs2, and igf-1. However, we did observe increased levels glycerol and free fatty acids released from adipocytes with reduced DBC1 following TNF (tumor necrosis factor) α stimulation. Although loss of DBC1 did not alter STAT5 transcriptional activity for the genes examined, it appears to modulate TNFα-mediated lipolysis in a STAT5-independent manner. In addition, DBC1 knockdown increased GLUT4 expression in murine fat cells but did not have a profound effect on TNFα-mediated changes in gene expression. On-going studies are being performed to elucidate the function of the DBC1/STAT5A interaction and to clarify the impact of DBC1 on lipolysis in adipocytes.


A. Able: None. A.J. Richard: None. J.M. Stephens: None.

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