Prion-like Properties of Short Isoforms of Human Chromatin Modifier PHC3

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Prion-like Properties of Short Isoforms of Human Chromatin Modifier PHC3. / Kachkin, Daniil ; Zelinsky, Andrew A.; Romanova, Nina V.; Kulichikhin, Konstantin Y.; Zykin, Pavel A.; Khorolskaya, Julia I.; Deckner, Zachery J.; Rubel, Aleksandr A.; Chernoff, Yury O.; Kajava, Andrey V.

In: International Journal of Molecular Sciences, Vol. 26, No. 4, 1512 , 11.02.2025.

Research output: Contribution to journal › Article › peer-review

BibTeX

@article{da8a314f7f7f4b85b640dc90cb4d4e06,

title = "Prion-like Properties of Short Isoforms of Human Chromatin Modifier PHC3",

abstract = "The formation of self-perpetuating protein aggregates such as amyloids is associated with various diseases and provides a basis for transmissible (infectious or heritable) protein isoforms (prions). Many human proteins involved in the regulation of transcription contain potentially amyloidogenic regions. Here, it is shown that short N-terminal isoforms of the human protein PHC3, a component of the chromatin-modifying complex PRC1 (Polycomb repressive complex 1), can form prion-like aggregates in yeast assays, exhibit amyloid properties in the E. coli-based C-DAG assay, and produce detergent-resistant aggregates when ectopically expressed in cultured human cells. Moreover, aggregates of short isoforms can sequester the full-length PHC3 protein, causing its accumulation in the cytosol instead of the nucleus. The introduction of an aggregating short PHC3 isoform alters the transcriptional profile of cultured human cells. It is proposed that the aggregation of short isoforms is involved in the feedback downregulation of PRC1 activity, leading to more open chromatin configuration. ",

keywords = "амилоиды, PHC3, Humans, Protein Isoforms/metabolism, Chromatin/metabolism, Prions/metabolism, Protein Aggregates, Polycomb-Group Proteins/metabolism, amyloid, C-DAG, prion, chromatin, PHC3",

author = "Daniil Kachkin and Zelinsky, {Andrew A.} and Romanova, {Nina V.} and Kulichikhin, {Konstantin Y.} and Zykin, {Pavel A.} and Khorolskaya, {Julia I.} and Deckner, {Zachery J.} and Rubel, {Aleksandr A.} and Chernoff, {Yury O.} and Kajava, {Andrey V.}",

year = "2025",

month = feb,

day = "11",

doi = "10.3390/ijms26041512",

language = "English",

volume = "26",

journal = "International Journal of Molecular Sciences",

issn = "1422-0067",

publisher = "MDPI AG",

number = "4",

}

RIS

TY - JOUR

T1 - Prion-like Properties of Short Isoforms of Human Chromatin Modifier PHC3

AU - Kachkin, Daniil

AU - Zelinsky, Andrew A.

AU - Romanova, Nina V.

AU - Kulichikhin, Konstantin Y.

AU - Zykin, Pavel A.

AU - Khorolskaya, Julia I.

AU - Deckner, Zachery J.

AU - Rubel, Aleksandr A.

AU - Chernoff, Yury O.

AU - Kajava, Andrey V.

PY - 2025/2/11

Y1 - 2025/2/11

N2 - The formation of self-perpetuating protein aggregates such as amyloids is associated with various diseases and provides a basis for transmissible (infectious or heritable) protein isoforms (prions). Many human proteins involved in the regulation of transcription contain potentially amyloidogenic regions. Here, it is shown that short N-terminal isoforms of the human protein PHC3, a component of the chromatin-modifying complex PRC1 (Polycomb repressive complex 1), can form prion-like aggregates in yeast assays, exhibit amyloid properties in the E. coli-based C-DAG assay, and produce detergent-resistant aggregates when ectopically expressed in cultured human cells. Moreover, aggregates of short isoforms can sequester the full-length PHC3 protein, causing its accumulation in the cytosol instead of the nucleus. The introduction of an aggregating short PHC3 isoform alters the transcriptional profile of cultured human cells. It is proposed that the aggregation of short isoforms is involved in the feedback downregulation of PRC1 activity, leading to more open chromatin configuration.

AB - The formation of self-perpetuating protein aggregates such as amyloids is associated with various diseases and provides a basis for transmissible (infectious or heritable) protein isoforms (prions). Many human proteins involved in the regulation of transcription contain potentially amyloidogenic regions. Here, it is shown that short N-terminal isoforms of the human protein PHC3, a component of the chromatin-modifying complex PRC1 (Polycomb repressive complex 1), can form prion-like aggregates in yeast assays, exhibit amyloid properties in the E. coli-based C-DAG assay, and produce detergent-resistant aggregates when ectopically expressed in cultured human cells. Moreover, aggregates of short isoforms can sequester the full-length PHC3 protein, causing its accumulation in the cytosol instead of the nucleus. The introduction of an aggregating short PHC3 isoform alters the transcriptional profile of cultured human cells. It is proposed that the aggregation of short isoforms is involved in the feedback downregulation of PRC1 activity, leading to more open chromatin configuration.

KW - амилоиды

KW - PHC3

KW - Humans

KW - Protein Isoforms/metabolism

KW - Chromatin/metabolism

KW - Prions/metabolism

KW - Protein Aggregates

KW - Polycomb-Group Proteins/metabolism

KW - amyloid

KW - C-DAG

KW - prion

KW - chromatin

KW - PHC3

UR - https://www.mendeley.com/catalogue/b52ef308-6867-332e-9afb-810d38b52bb9/

U2 - 10.3390/ijms26041512

DO - 10.3390/ijms26041512

M3 - Article

C2 - 40003978

VL - 26

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1422-0067

IS - 4

M1 - 1512

ER -

ID: 132391957