Question

Can anyone considerably dumb down what this abstract is telling me? I feel like reading this is like reading Latin to me. Can someone help me break down what is being said. Thank you so much.

Methyltransferase Set7/9 regulates p53 activity by interacting with Sirtuin 1 (SIRT1)

Numerous studies indicate that Sirtuin 1 (SIRT1), a mammalian nicotinamide adenine dinucleotide (NAD+ )-dependent histone deacetylase (HDAC), plays a crucial role in p53-mediated stress responses by deacetylating p53. Nevertheless, the acetylation levels of p53 are dramatically increased upon DNA damage, and it is not well understood how the SIRT1–p53 interaction is regulated during the stress responses. Here, we identified Set7/9 as a unique regulator of SIRT1. SIRT1 interacts with Set7/9 both in vitro and in vivo. In response to DNA damage in human cells, the interaction between Set7/9 and SIRT1 is significantly enhanced and coincident with an increase in p53 acetylation levels. Importantly, the interaction of SIRT1 and p53 is strongly suppressed in the presence of Set7/9. Consequently, SIRT1-mediated deacetylation of p53 is abrogated by Set7/9, and p53-mediated transactivation is increased during the DNA damage response. Of note, whereas SIRT1 can be methylated at multiple sites within its N terminus by Set7/9, a methylation-defective mutant of SIRT1 still retains its ability to inhibit p53 activity. Taken together, our results reveal that Set7/9 is a critical regulator of the SIRT1-p53 interaction and suggest that Set7/9 can modulate p53 function indirectly in addition to acting through a methylation-dependent mechanism.

p21waf1/cip1 | posttranslational modifications | tumor suppression

I think because there are so many names and players, and being unfamiliar with the terms, it's hard for me to understand.

Any help would be greatly appreciated. Thank you. I will gladly give a good rating.

Answer 1

First, let us look at the enzymes and proteins involved in the study:

Methyltransferase: This is an enzyme that transfers methyl groups from the substrate to form the product.

Deacetylase: Enzyme that removes acetyl groups from the substrate

p53: p53 is a transcription factor that regulates the expression of genes when the cells experience stress. This is also known as the ‘tumor suppressor protein’ found in the nucleus of all cells. This protein is ‘acetylated’ by the enzyme Histone acetyl transferase the action of which results in the activation of p53 to function in the cell; whereas Histone deacetylase (HDAC) downregulates the actvity of p53. Sirutin 1 is a histone deacetylase known to regulate p53.

Set 7/9 : This is a ‘methyl transferase’ that methylates Sirutin1

Sirutin 1 is known to suppress the activity of p53 by deacetylation. However, when Set 7/9 is present, the methylation of Sirutin 1 by Set 7/9 renders Sirutin 1 to be unable to interact with p53, and therefore p53 is not deacetylated, (but acetylated and activated by Histone acetyl transferase) and its activity is NOT suppressed.

Sirutin 1 suppresses the activity of p53 and Set 7/9 suppresses the activity of Sirutin 1.

So the study concludes that the enzyme Set 7/9 indirectly regulates the action of p53 by interacting with Sirutin1.