Journal
DNA REPAIR
Volume 65, Issue -, Pages 42-46Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.dnarep.2018.03.004
Keywords
Transformation; Small GTPase; Protein kinase; DNA repair; Small molecule inhibitor
Categories
Funding
- UNAM [PAPIIT IN213218]
- CONACyT [252444]
- Direccion General de Asuntos del Personal Academico
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p21-activated kinase 1 (PAK1) is a serine/threonine kinase activated by the small GTPases Racl and Cdc42. It is located in the chromosome 11q13 and is amplified and/or overexpressed in several human cancer types including 25-30% of breast tumors. This enzyme plays a pivotal role in the control of a number of fundamental cellular processes by phosphorylating its downstream substrates. In addition to its role in the cytoplasm, it is well documented that PAK1 also plays crucial roles in the nucleus participating in mitotic events and gene expression through its association and/or phosphorylation of several transcription factors, transcriptional co-regulators and cell cycle-related proteins, including Aurora kinase A (AURKA), polo-like kinase 1 (PLK1), the forkhead transcription factor (FKHR), estrogen receptor alpha (ER alpha), and Snail. More recently, PAK signaling has emerged as a component of the DNA damage response (DDR) as PAK1 activity influences the cellular sensitivity to ionizing radiation and promotes the expression of several genes involved in the Fanconi Anemia/BRCA pathway. This review will focus on the nuclear functions of PAK1 and its role in the regulation of DNA damage repair.
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