Protein polybromo-1 (PB1) also known as BRG1-associated factor 180 (BAF180) is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
that in humans is encoded by the ''PBRM1''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
Structure and function
Human PBRM1 is one of three unique components of the
SWI/SNF
In molecular biology, SWI/SNF (SWItch/Sucrose Non-Fermentable), is a subfamily of ATP-dependent chromatin remodeling complexes, which is found in eukaryotes. In other words, it is a group of proteins that associate to remodel the way DNA is packa ...
-B (PBAF) chromatin-remodeling complex, which contains at least
SMARCA4
Transcription activator BRG1 also known as ATP-dependent chromatin remodeler SMARCA4 is a protein that in humans is encoded by the ''SMARCA4'' gene.
Function
The protein encoded by this gene is a member of the SWI/SNF family of proteins and ...
/BRG1,
SMARCB1
SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 is a protein that in humans is encoded by the ''SMARCB1'' gene.
Function
The protein encoded by this gene is part of a complex that relieves repress ...
/SNF5/INI1/BAF47,
ACTL6A
Actin-like protein 6A is a protein that in humans is encoded by the ''ACTL6A'' gene.
Function
This gene encodes a family member of actin-related proteins (ARPs), which share significant amino acid sequence identity to conventional actins. Bot ...
/BAF53A or
ACTL6B
Actin-like protein 6B is a protein that in humans is encoded by the ''ACTL6B'' gene.
Function
The protein encoded by this gene is a member of a family of actin-related proteins (ARPs) which share significant amino acid sequence identity to conven ...
/BAF53B,
SMARCE1
SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1 is a protein that in humans is encoded by the ''SMARCE1'' gene.
Function
The protein encoded by this gene is part of the large ATP-dependent chromati ...
/BAF57,
SMARCD1
SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily D member 1 is a protein that in humans is encoded by the ''SMARCD1'' gene.
The protein encoded by this gene is a member of the SWI/SNF family of proteins, whose me ...
/BAF60A,
SMARCD2
SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily D member 2 is a protein in humans that is encoded by the ''SMARCD2'' gene.
The protein encoded by this gene is a member of the SWI/SNF family of proteins, whose me ...
/BAF60B, and
actin
Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of ...
.
Chicken PB1 possesses 5
bromodomain
A bromodomain is an approximately 110 amino acid protein domain that recognizes acetylated lysine residues, such as those on the ''N''-terminal tails of histones. Bromodomains, as the "readers" of lysine acetylation, are responsible in transducin ...
s, 2 bromo-adjacent homology (BAH) domains, and 1 truncated
high-mobility group
High-Mobility Group or HMG is a group of chromosomal proteins that are involved in the regulation of DNA-dependent processes such as
transcription, replication, recombination, and DNA repair. History and name
HMG proteins were originally isolate ...
(HMG) motif. cPB1 is also homologous to yeast Rsc1, Rsc2, and Rsc4, essential proteins that are required for
cell cycle
The cell cycle, or cell-division cycle, is the sequential series of events that take place in a cell (biology), cell that causes it to divide into two daughter cells. These events include the growth of the cell, duplication of its DNA (DNA re ...
progression through
mitosis
Mitosis () is a part of the cell cycle in eukaryote, eukaryotic cells in which replicated chromosomes are separated into two new Cell nucleus, nuclei. Cell division by mitosis is an equational division which gives rise to genetically identic ...
.
Clinical significance
PBRM1 is thought to be a
tumor suppressor gene
A tumor suppressor gene (TSG), or anti-oncogene, is a gene that regulates a cell (biology), cell during cell division and replication. If the cell grows uncontrollably, it will result in cancer. When a tumor suppressor gene is mutated, it results ...
in many cancer subtypes largely due to the mutational pattern. Most notably, mutations and copy number alterations in ''PBRM1'' are highly prevalent in
clear cell renal cell carcinoma
Clear-cell renal-cell carcinoma (CCRCC) is a type of renal-cell carcinoma.
Genetics Cytogenetics
* Alterations of chromosome 3p segments occurs in 70–90% of CCRCCs
* Inactivation of von Hippel–Lindau disease ( VHL) gene by gene mutation a ...
(ccRCC).
Role renal carcinoma
Loss of function mutations in ''PBRM1'' often co-occur with loss of function mutations in the ''
VHL'' gene in
clear cell renal cell carcinoma
Clear-cell renal-cell carcinoma (CCRCC) is a type of renal-cell carcinoma.
Genetics Cytogenetics
* Alterations of chromosome 3p segments occurs in 70–90% of CCRCCs
* Inactivation of von Hippel–Lindau disease ( VHL) gene by gene mutation a ...
(ccRCC). The inactivation of PBRM1 in combination with biallelic loss of VHL has been shown to potentiate
HIF1α
Hypoxia-inducible factor 1-alpha, also known as HIF-1-alpha, is a subunit of a heterodimeric transcription factor hypoxia-inducible factor 1 (HIF-1) that is encoded by the ''HIF1A'' gene. The Nobel Prize in Physiology or Medicine 2019 was awar ...
signaling and activate the pro-tumorigenic NF-κB pathway. Genetic loss of ''PBRM1'' is thought to underlie the early initiation of ccRCC due to the sufficiency of conditional deletion of ''Pbrm1'' and ''Vhl'' for renal carcinomagenesis in mice. While several studies have identified a favorable outcomes among advanced ccRCC cases with ''PBRM1'' mutations when treated with
immune checkpoint inhibitors, there is still debate about the utility of ''PBRM1'' status as a biomarker for response to ICI therapy.
References
Further reading
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{{PDB Gallery, geneid=55193