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Related Experiment Video

Updated: May 9, 2026

Purification of Ubiquitinated p53 Proteins from Mammalian Cells

Purification of Ubiquitinated p53 Proteins from Mammalian Cells

Published on: March 21, 2022

The p53-PUMA axis suppresses iPSC generation.

Yanxin Li¹, Haizhong Feng, Haihui Gu

¹State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Center for Stem Cell Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing Road No. 288, Tianjin 300020, China.

Nature Communications

|July 23, 2013

Summary

The tumor suppressor p53 pathway, including PUMA, negatively impacts induced pluripotent stem cell generation. Targeting PUMA, not p21, may improve reprogramming efficiency for therapeutic applications.

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Area of Science:

Cell biology
Stem cell research
Cancer biology

Background:

The mechanisms of induced pluripotent stem cell (iPSC) reprogramming are not fully understood.
The Trp53 (p53) pathway, known for its role in tumor suppression, can inhibit iPSC generation, partly through p21Cdkn1a (p21)-mediated cell cycle arrest.

Purpose of the Study:

To investigate the role of PUMA, a pro-apoptotic factor in the p53 pathway, in somatic cell reprogramming.
To compare the function of PUMA with p21 in the context of p53-mediated suppression of iPSC generation.

Main Methods:

Utilized mouse models deficient in PUMA, p21, and p53.
Assessed the impact of these genetic deficiencies on the efficiency of induced pluripotent stem cell induction.
Evaluated DNA damage and chromosomal aberrations in iPSCs derived from these mouse models.

Main Results:

PUMA acts as an independent mediator of p53's negative effect on iPSC induction.
PUMA deficiency enhanced iPSC survival, reducing DNA damage and chromosomal aberrations.
Conversely, loss of p21 or p53 led to opposite outcomes, hindering iPSC generation.

Conclusions:

PUMA represents a distinct and potentially more favorable therapeutic target within the p53 pathway for improving iPSC generation.
Targeting PUMA could have significant implications for advancing the therapeutic potential of iPSCs.