ERK7
ERK7 (MAPK15, also known as ERK8) is an atypical member of the mitogen-activated protein kinase (MAPK) family that differs from conventional MAPKs because it does not operate through a classical three-tiered MAPKKK-MAPKK-MAPK signaling cascade and exhibits distinct regulatory mechanisms[1][2]. ERK7 functions as a conserved regulator of cellular homeostasis, integrating signaling pathways that control ciliogenesis, autophagy, cell growth, metabolism, and genome maintenance[1][3][4]. Mechanistically, ERK7 is required for the formation and maintenance of primary cilia and regulates the localization of ciliary proteins involved in cilium structure, transport, and signaling, highlighting a conserved role in ciliary biology across species[4][5]. In parallel, ERK7 promotes autophagic processes through interactions with LC3 and GABARAP family proteins, linking nutrient-responsive signaling to intracellular quality-control pathways[3]. ERK7 also contributes to genomic integrity by protecting cellular DNA maintenance machinery, thereby connecting stress responses with genome surveillance mechanisms[1]. In disease-relevant models, altered MAPK15 activity has been associated with tumorigenic phenotypes, including enhanced cell proliferation, maintenance of genomic stability, and autophagy-dependent support of cancer cell survival[6]. Compared with classical ERK isoforms such as ERK1/2, ERK7 displays unique structural and signaling properties and remains one of the least characterized MAPKs, making it an important experimental model for studying non-canonical MAPK signaling and cilia-associated biology[1][2].
References:
- [1]. Deniz O, et al. Cellular and physiological roles of the conserved atypical MAP kinase ERK7. FEBS Lett. 2023 Mar;597(5):601-607. [Content Brief]
- [2]. Tang Y, et al. Tip60-dependent acetylation of p53 modulates the decision between cell-cycle arrest and apoptosis. Mol Cell. 2006 Dec 28;24(6):827-39. [Content Brief]
- [3]. Klaric AS, et al. Neuropsychological development in preschool children born with asymmetrical intrauterine growth restriction and impact of postnatal head growth. J Child Neurol. 2013 Jul;28(7):867-73. [Content Brief]
- [4]. Kazatskaya A, et al. Primary Cilium Formation and Ciliary Protein Trafficking Is Regulated by the Atypical MAP Kinase MAPK15 in Caenorhabditis elegans and Human Cells. Genetics. 2017 Dec;207(4):1423-1440. [Content Brief]
- [5]. Wang CY, et al. New streams and springs after the 2014 Mw6.0 South Napa earthquake. Nat Commun. 2015 Jul 9;6:7597. [Content Brief]
- [6]. Rossi M, et al. MAPK15 upregulation promotes cell proliferation and prevents DNA damage in male germ cell tumors. Oncotarget. 2016 Apr 12;7(15):20981-98. [Content Brief]
