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Transcription Factors in the Akt Pathway Proteins

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Transcription Factors in the Akt Pathway Proteins

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Transcription Factors in the Akt Pathway Proteins Background

In molecular biology, transcription factors (TF) (or sequence-specific DNA binding factors) are proteins that control the rate of transcription of genetic information from DNA to messenger RNA by binding to specific DNA sequences. The function of TFs is to regulate - turn genes on and off to ensure they are expressed in the right cells at the right time and in the right amount throughout the life cycle of the cell and organism. The TF group acts in a coordinated manner to direct cell division, cell growth and cell death throughout life; cell migration and organization during embryonic development (physical planning); and intermittent response to signals from outside the cell, such as hormones. There are as many as 2,600 TFs in the human genome.

TFs act alone or in conjunction with other proteins in the complex by promoting (as an activator) or blocking (as a repressor) RNA polymerase (an enzyme that transcribes genetic information from DNA to RNA) to the recruitment of specific genes. A defining feature of TF is that they contain at least one DNA binding domain (DBD) attached to a particular DNA sequence adjacent to the gene they regulate. The TF is classed according to its DBD grouping. Other proteins such as coactivators, chromatin remodeling proteins, histone acetyltransferases, histone deacetylases, kinases and methylases are also required for gene regulation, but lack DNA binding domains and are therefore not TF. TF is of great interest to medicine because TF mutations can cause specific diseases and drugs may potentially target them.

Mechanism

Transcription factors bind to enhancers or promoter regions of DNA adjacent to their regulated genes. According to transcription factors, transcription of adjacent genes can be upregulated or downregulated. Transcription factors use a variety of mechanisms to regulate gene expression. These mechanisms include:

  • Stabilize or block the binding of RNA polymerase to DNA
  • Catalytic acetylation or deacetylation of histones. Transcription factors can directly do this or recruit other proteins with this catalytic activity. Many transcription factors use one or the other of two opposite mechanisms to regulate transcription:
  • Histone acetyltransferase (HAT) activity - acetylation of histones, weakening the binding of DNA to histones, making DNA easier to transcribe, thereby upregulating transcription.
  • Histone deacetylase (HDAC) activity - Deacetylation of histones, enhanced DNA binding to histones, making DNA less transcribed, thereby downregulating transcription.
  • Recruit coactivator or corepressor proteins to the transcription factor DNA complex.

Function

Transcription factors are one of the proteomes that read and interpret genetic "blueprints" in DNA. They bind to DNA and help initiate the process of increasing or decreasing gene transcription. Therefore, they are critical to many important cellular processes.

Transcription Factors in the Akt Pathway

Signal transduction often culminates in the activation of transcription factors, a specialized subset of proteins capable of interacting with DNA to either up- or downregulate the transcription of genes. Transcription factor binding is often specific for certain DNA sequences. They are highly regulated with respect to cytoplasmic vs. nuclear localization, stabilization, and post-translational modification. The transcription factors listed below have all been associated with Akt pathway activation, which promotes cell growth, survival, proliferation, autophagy, and metabolism. The activity of these transcription factors is either up- or downregulated by Akt signaling.

References:

1. Nikolov DB.; et al. RNA polymerase II transcription initiation: a structural view". Proceedings of the National Academy of Sciences of the United States of America, 1997, 94 (1): 15-22.

2. Wintjens R.; et al. Structural classification of HTH DNA-binding domains and protein-DNA interaction modes. Journal of Molecular Biology. 1996, 262 (2): 294-313.

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