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Nonhistone Human Chromatin Protein PC4 Is Critical for Genomic Integrity and Negatively Regulates Autophagy

Nonhistone Human Chromatin Protein PC4 Is Critical for Genomic Integrity and Negatively Regulates Autophagy

Sweta Sikder, Sujata Kumari, Pallabi Mustafi, Nisha Ramdas, Swatishree Padhi, Arka Saha, Utsa Bhaduri, Birendranath Banerjee, Ravi Manjithaya, Tapas K Kundu

FEBS J. 2019 Nov;286(22):4422-4442.

PMID: 31169983

Abstract:

Multifunctional human transcriptional positive co-activator 4 (PC4) is a bona fide nonhistone component of the chromatin and plays a pivotal role in the process of chromatin compaction and functional genome organization. Knockdown of PC4 expression causes a drastic decompaction which leads to open conformation of the chromatin, and thereby altered nuclear architecture, defects in chromosome segregation and changed epigenetic landscape. Interestingly, these defects do not induce cellular death but result in enhanced cellular proliferation, possibly through enhanced autophagic activity. Moreover, PC4 depletion confers significant resistance to gamma irradiation. Exposure to gamma irradiation further induced autophagy in these cells. Inhibition of autophagy by small molecule inhibitors as well as by silencing of a critical autophagy gene drastically reduces the ability of PC4 knockdown cells to survive. On the contrary, complementation with wild-type PC4 could reverse this phenomenon, confirming the process of autophagy as the key mechanism for radiation resistance in the absence of PC4. These data connect the unexplored role of chromatin architecture in regulating autophagy during stress conditions such as radiation.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42414931	PC4, wild type human			Price

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