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Publication : Acute myeloid leukemia-associated Mkl1 (Mrtf-a) is a key regulator of mammary gland function.

First Author  Sun Y Year  2006
Journal  Mol Cell Biol Volume  26
Issue  15 Pages  5809-26
PubMed ID  16847333 Mgi Jnum  J:111560
Mgi Id  MGI:3654403 Doi  10.1128/MCB.00024-06
Citation  Sun Y, et al. (2006) Acute myeloid leukemia-associated Mkl1 (Mrtf-a) is a key regulator of mammary gland function. Mol Cell Biol 26(15):5809-26
abstractText  Transcription of immediate-early genes--as well as multiple genes affecting muscle function, cytoskeletal integrity, apoptosis control, and wound healing/angiogenesis--is regulated by serum response factor (Srf). Extracellular signals regulate Srf in part via a pathway involving megakaryoblastic leukemia 1 (Mkl1, also known as myocardin-related transcription factor A [Mrtf-a]), which coactivates Srf-responsive genes downstream of Rho GTPases. Here we investigate Mkl1 function using gene targeting and show the protein to be essential for the physiologic preparation of the mammary gland during pregnancy and the maintenance of lactation. Lack of Mkl1 causes premature involution and impairs expression of Srf-dependent genes in the mammary myoepithelial cells, which control milk ejection following oxytocin-induced contraction. Despite the importance of Srf in multiple transcriptional pathways and widespread Mkl1 expression, the spectrum of abnormalities associated with Mkl1 absence appears surprisingly restricted.
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