4.6 Article

Megakaryoblastic leukemia protein-1 (MKL1): Increasing evidence for an involvement in cancer progression and metastasis

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PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.biocel.2010.08.014

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Megakaryoblastic leukemia-1; Myocardin-related transcription factors; Cancer; Metastasis; Actin

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Megakaryoblastic leukemia protein-1 (MKL1), also termed MAL, MRTF-A, and BSAC, belongs to the MRTF family of transcription factors that share evolutionary conserved domains required for actin-binding, homo- and heterodimerization, high-order chromatin organization and transcriptional activation. MKL1 regulates many processes, including muscle cell differentiation, cardiovascular development, remodeling of neuronal networks in the developing and adult brain, megakaryocytic differentiation and migration, modulation of cellular motile functions and epithelial-mesenchymal transition. Moreover, deregulation by genetic alterations and/or altered expression of MKL1 can contribute to a number of pathological processes such as coronary artery disease, sarcopenia, acute megakaryoblastic leukemia, and cancer. In this article, we review the structure, regulation and biological functions of MKL1. In addition, we discuss recent evidence that strongly suggests a dual role for MKL1 in oncogenic mechanisms, as a tumor-promoting or tumor-suppressing molecule. Future studies will be necessary to evaluate the potential clinical implications of MKL1 expression and activation in cancer. (C) 2010 Elsevier Ltd. All rights reserved.

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