Structural Biochemistry, Oct Proteins

Oct1 and Oct4 are two transcription factors that are key regulators of pluripotency and stem cells and they are the proteins most involved with adult stem cells and cancer. Oct proteins are defined by their ability to interact with a DNA sequence known as the ‘octamer motif’. Oct4 and Oct1 belong to a group of proteins called POU. POU proteins are divided into six classes (POU1 to POU6) based on their DNA binding domains. In this, it can be seen that Oct 4 is an outlier as the DNA sequence it recognizes is different than the other proteins in the POU group. The Oct proteins, in general, can also recognize non octamer sequences due to the conformational flexibility of their linker domain.

Oct4

Oct 4 is the main regulator of pluriotency. Its expression is extremely restricted and limited to the early embroyic development stage. Oct4 is also necessary for ES cell phenotype and for the development of a cell past the blastocyst stage. Because Oct4 is responsible for pluripotency, elevated or reduced expression can lead to excessive changes in the amount of cells. Therefore, the Oct4 protein is highly regulated at multiple levels. While Oct4 is currently used as a min component to generate iPS(induced pluripotent stem) cells there is still a long way to go before iPS can be widely used to generate all types of cells. It has also been found that aggressive human breast carcinomas are devoid of consistent Oct4 expression. Instead, Oct4 paralogs that assume Oct4-like functions are found in these tissues.

Oct1

Oct 1 shares the same functions, targets and regulation of common genes however it cannot substitute for Oct4 in the generation of pluripotency cells. The protein is mainly expressed in adult and embryonic tissues. Because of its function, Oct1 is also heavily regulated on multiple levels. Recent research has pointed to the idea that Oct1 might play a part in regulating its own synthesis. Oct1 deficient cells are extremely sensitive to glucose withdrawal and oxidative stress agents. The metabolic changes in Oct1 deficient cells directly contrast the metabolic changes in tumor cells, implying that Oct1 proteins might have a cancer-protecting effect. Because of this Oct1 is currently one of the main avenues for cancer research. Currently, it has been seen in lab that loss of Oct1 reduces oncogenic transformation in culture and cancer incidences in mouse models.

References

Kang, J. (2009) Stem cells, stress, metabolism and cancer: a drama in two Octs. Cell Press, 491-499

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