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

Sun Y, Boyd K, Xu W, Ma J, Jackson CW, Fu A, Shillingford JM, Robinson GW, Hennighausen L, Hitzler JK, Ma Z, Morris SW
Mol Cell Biol. 2006 26 (15): 5809-26

PMID: 16847333 · PMCID: PMC1592762 · DOI:10.1128/MCB.00024-06

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.

MeSH Terms (28)

Animals Animals, Newborn Apoptosis Child Failure to Thrive Female Gene Expression Profiling Gene Expression Regulation Gene Targeting Heart Humans Infant Lactation Leukemia, Megakaryoblastic, Acute Male Mammary Glands, Animal Mice Mice, Inbred C57BL Mice, Knockout Milk Myocytes, Cardiac Oligonucleotide Array Sequence Analysis Oxytocin Pregnancy Prolactin Serum Response Factor STAT3 Transcription Factor Trans-Activators

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