Abstract
Microtubule severing, which is highly critical for the survival of both mitotic and post-mitotic cells, has to be precisely adjusted by regulating the expression levels of severing proteins, katanin and spastin. Even though severing mechanism is relatively well-studied, there are limited studies for the transcriptional regulation of microtubule severing proteins. In this study, we identified the main regulatory region of KATNA1 gene encoding katanin-p60 as 5’ UTR, which has a key role for its expression, and showed Elk1 binding to KATNA1. Furthermore, we identified that Elk1 decreased katanin-p60 and spastin protein expressions, while mRNA levels were increased upon Elk1 overexpression. In addition, SUMOylation is a known post-translational modification regulating Elk1 activity. A previous study suggested that K230, K249, K254 amino acids in the R domain are the main SUMOylation sites; however, we identified that these amino acids are neither essential nor substantial for Elk1 SUMOylation. Also, we determined that KATNA1 methylation results in the reduction of Elk1 binding whereas SPG4 methylation does not. Together, our findings emphasizing the impacts of both transcriptional and post-transcriptional regulations of katanin-p60 and spastin suggest that Elk1 has a key role for differential expression patterns of microtubule severing proteins, thereby regulating cellular functions through alterations of microtubule organization.
Highlights
Microtubules are responsible for many important cellular events in mitotic cells, such as cell division, localization of organelles and migration, as well as neuronal branching, axonal growth and neuronal morphogenesis in neurons
Katanin is a heterodimeric protein consisting of 60 kDa and 80 kDa polypeptides, which are encoded by KATNA1 and KATNB1 genes, respectively [2]
Initiation of transcription requires the addition of RNA polymerase II to preinitiation complex (PIC) at the core promoter, which is defined as the region from -40 bp upstream to +40 bp downstream of transcription start site of genes
Summary
Microtubules are responsible for many important cellular events in mitotic cells, such as cell division, localization of organelles and migration, as well as neuronal branching, axonal growth and neuronal morphogenesis in neurons. And disassembly property of microtubules, which is called “dynamic instability” is required to carry out these processes. Microtubule severing proteins such as katanin and spastin promote the dynamic nature of microtubules by generating internal breakages within the microtubule lattice [1,2,3,4]. Spastin is a monomer encoded by SPG4 ( known as SPAST) gene [5]. Both katanin and spastin proteins belong to ATPases associated with diverse cellular Activities (AAA) protein family [6]
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