Transcription factor doubling as a structural protein identified in world’s first.


Structural proteins perform much like their name suggests, they maintain cell shape and make up connective tissues like cartilage and bone.  Telling a cell biologist that a structural protein is doubling as a transcription factor will not be believed as it’s never been seen before.  Now, researchers at Washington State University, Penn State, the Chinese Academy of Sciences, Zhejiang Sci-Tech University and the University of Texas have discovered that a well known protein ATF5, or Activating Transcription Factor 5, which controls how often specific genes are expressed, is also acting as a structural protein. The opensource study is published in the journal Cell.

Previous studies show that ATF5 regulates genes that control cell survival. The current study identified a part this protein is playing, within the region of the cell called the centrosome, that is not related to its transcription factor role.  The researchers note that the discovery provides the first evidence of structural interactions within the centrosome and the role of ATF5, which was strategically located within the centrosome and playing a totally different role than previously understood.

The team explain that the centrosome is the cell component vital to successful cell division and duplication, which affect a wide spectrum of larger processes from healing to cancer growth to fighting off disease.  They go on to add that failure of centrosome duplication can result in malformation of mitotic spindles, causing a variety of genomic instabilities. Malformed cells contribute to tumour development and conditions such as dwarfism, ciliopathy, microcephaly and problems with cilia movement, which is why cells observed in the current study included ovary cancer, breast cancer and glioma (brain tumour).

Earlier studies show that cilia work like antenna and communicate with the rest of the cell to move it toward nutrients, however, knowledge is limited as to how cilia work. The data findings helps connect the dots, with the lab hoping this research will expand understanding of cell survival.

In a previous study from the team, ATF5 was tagged a fluorescent protein produced by jellyfish.  ATF5 was discovered in an area of the cell that didn’t seem to make sense. Therefore the researchers wanted to show that the presence of ATF5 outside its ‘normal place’ was irrelevant.  However, it became apparent it had real purpose and ultimately, became a big discovery.

Source:  Washington State University

 

Although it is known that the centrioles play instructive roles in pericentriolar material (PCM) assembly and that the PCM is essential for proper centriole formation, the mechanism that governs centriole-PCM interaction is poorly understood. Here, we show that ATF5 forms a characteristic 9-fold symmetrical ring structure in the inner layer of the PCM outfitting the proximal end of the mother centriole. ATF5 controls the centriole-PCM interaction in a cell-cycle- and centriole-age-dependent manner. Interaction of ATF5 with polyglutamylated tubulin (PGT) on the mother centriole and with PCNT in the PCM renders ATF5 as a required molecule in mother centriole-directed PCM accumulation and in PCM-dependent centriole formation. ATF5 depletion blocks PCM accumulation at the centrosome and causes fragmentation of centrioles, leading to the formation of multi-polar mitotic spindles and genomic instability. These data show that ATF5 is an essential structural protein that is required for the interaction between the mother centriole and the PCM.  ATF5 Connects the Pericentriolar Materials to the Proximal End of the Mother Centriole.  Liu et al 2015

Although it is known that the centrioles play instructive roles in pericentriolar material (PCM) assembly and that the PCM is essential for proper centriole formation, the mechanism that governs centriole-PCM interaction is poorly understood. Here, we show that ATF5 forms a characteristic 9-fold symmetrical ring structure in the inner layer of the PCM outfitting the proximal end of the mother centriole. ATF5 controls the centriole-PCM interaction in a cell-cycle- and centriole-age-dependent manner. Interaction of ATF5 with polyglutamylated tubulin (PGT) on the mother centriole and with PCNT in the PCM renders ATF5 as a required molecule in mother centriole-directed PCM accumulation and in PCM-dependent centriole formation. ATF5 depletion blocks PCM accumulation at the centrosome and causes fragmentation of centrioles, leading to the formation of multi-polar mitotic spindles and genomic instability. These data show that ATF5 is an essential structural protein that is required for the interaction between the mother centriole and the PCM. ATF5 Connects the Pericentriolar Materials to the Proximal End of the Mother Centriole. Liu et al 2015

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