Tissue-specific expression of p73 and p63 isoforms in human tissues

Clayton B Marshall,J Scott Beeler,Paula Gonzalez-Ericsson,Melinda E Sanders,Kelli L Boyd,Violeta Sanchez,Brian D Lehmann,Jennifer A Pietenpol

doi:10.1038/s41419-021-04017-8

Abstract

p73 and p63 are members of the p53 family that exhibit overlapping and distinct functions in development and homeostasis. The evaluation of p73 and p63 isoform expression across human tissue can provide greater insight to the functional interactions between family members. We determined the mRNA isoform expression patterns of TP73 and TP63 across a panel of 36 human tissues and protein expression within the highest-expressing tissues. TP73 and TP63 expression significantly correlated across tissues. In tissues with concurrent mRNA expression, nuclear co-expression of both proteins was observed in a majority of cells. Using GTEx data, we quantified p73 and p63 isoform expression in human tissue and identified that the α-isoforms of TP73 and TP63 were the predominant isoform expressed in nearly all tissues. Further, we identified a previously unreported p73 mRNA product encoded by exons 4 to 14. In sum, these data provide the most comprehensive tissue-specific atlas of p73 and p63 protein and mRNA expression patterns in human and murine samples, indicating coordinate expression of these transcription factors in the majority of tissues in which they are expressed.

Highlights

INTRODUCTION p73 and p63 are members of the p53 family of sequence-specific transcription factors that directly regulate differentiation, cell cycle, proliferation, DNA repair, and apoptosis [1–5]. p73 and p63 bind similar consensus DNA binding sites [6, 7]; but diverge in their regulation of gene targets [8–11]
We found that full-length E8 was the Previous publications have examined the protein expression predominant TP63 isoform expressed (~70%) and the shortened patterns of p73 and p63 in select murine and human tissues, variant of exon 8 (E8s) was expressed at lower levels (~30%)
We detected transcriptome profiling has made it possible to quantitatively a RAMPAGE peak at the 5′ end of TP73 exon 3a (E3a), in testis (Fig. 4A), the only tissue that expresses significant levels of a transcript composed of only E3a and exon 4 (E4)

Summary

DISCUSSION

The analysis of p73 and p63 has been challenging due to the lack of isoform-specific antibodies and the large number of isoforms that can be generated from each gene. E4 to either E2 or E1 in the GTEx data; rather, we observed a unique TSS in the intronic region directly upstream of E4, Analysis of Tp73 and Tp63 mRNA in murine tissues To extend our p63 and p73 isoform findings to another organism, and analyze primary tissue instead of in silico data sets, we potentially generating a putative UTR upstream of an early E4 methionine. This study provides the most extensive analyses showed that protein expression in murine skin, vagina, bioinformatic analysis of TP73 and TP63 mRNA isoform expression mammary gland, and muscle tissue correlates highly with mRNA across human tissues to date coupled with an atlas of protein expression Isoform expression for each tissue was calculated as the mean

MATERIALS AND METHODS

CODE AVAILABILITY

Findings

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