Lipid News

PI-PLC β1 in differentiation
and disease

Lucio Cocco
By Lucio Cocco
March 1, 2017

Evidence from several laboratories has highlighted the presence of autonomous nuclear inositol lipid metabolism. The evidence suggests that lipid molecules are important components of signaling pathways operating within the nucleus. The findings are important, given the fact that nuclear signaling activity controls cell growth and differentiation.

Inositide-specific phospholipase C plays a role in MDS and a form of muscular dystrophy.IMAGE PROVIDED BY LUCIO COCCO

Among the nuclear enzymes involved in this system, inositide-specific phospholipase C, or PI-PLC, β1 is one of the most extensively studied enzymes. Besides the studies on its signaling activity, clinically oriented studies have shown that a mono-allelic deletion of the PI-PLCβ1 gene is associated with the evolution of myelodysplastic syndromes, or MDS, into acute myeloid leukemia. Studies also have showed that increased PI-PLCβ1 gene expression, due to reduced methylation and reactivation of its promoter, associates with responsiveness to demethylating agents, such as azacitidine, in MDS. Extensive clinical and molecular evaluation have aimed to establish a predictive role of increased PI-PLCβ1 gene expression during the first three cycles of treatment with the demethylating drug azacitidine. The data obtained hint at PI-PLCβ1 expression as a useful tool for the early identification of a subgroup of patients with a higher probability of response to azacitidine. These data suggest also a possible involvement of nuclear PI-PLCβ1 in the early stages of hemopoiesis and specifically in the control of cell-cycle progression in progenitor hemopoietic cells. Nuclear PI-PLCβ1 also is involved in myogenic differentiation.

Indeed, nuclear PI-PLCβ1 plays a crucial role in the initiation of the genetic program responsible for muscle differentiation: the enzyme activates the cyclin D3 promoter during the differentiation of myoblasts to myotubes. This indicates that PI-PLCβ1 is essential for cyclin D3 promoter activation and gene transcription through c-jun/AP1.

Myotonic dystrophy is the most prevalent form of muscular dystrophy in adults. DM type 1 and type 2 are dominantly inherited multisystem disorders. DM1 is triggered by the pathological expansion of a CTG triplet repeat in the gene coding for DMPK, the dystrophia myotonica-protein kinase. A CCTG tetranucleotide repeat expansion in the ZNF9 gene, which encodes a CCHC-type zinc-finger protein, causes DM2. Unlike in normal myotubes, the level of expression of PI-PLCβ1 in DM1 and DM2 cells already is elevated in proliferating cells. Treatment with insulin induces a dramatic decrease in the amount of PI-PLCβ1. During differentiation, cyclin D3 and myogenin are elevated in normal myotubes. When DM1 and DM2 cells are induced to differentiate, they do not show any increase in these proteins. Forced expression of PI-PLCβ1 in DM1 and DM2 cells increases the expression of differentiation markers myogenin and cyclin D3 and enhances fusion of DM myoblasts. These results highlight again that nuclear PI-PLCβ1 expression is a key player in myoblast differentiation, functioning as a positive regulator in the correction of delayed differentiation of human skeletal muscle.

Enjoy reading ASBMB Today?

Become a member to receive the print edition monthly and the digital edition weekly.

Learn more
Lucio Cocco
Lucio Cocco

Lucio Cocco is a professor and head of the cellular signaling laboratory in the department of biomedical sciences at the University of Bologna in Italy.

Related articles

‘Fatty retina’: A root cause of vision loss in diabetes?
Clay Semenkovich & Rithwick Rajagopal
Targeting cardiolipin modification in a genetic disorder
Arianna F. Anzmann, Olivia Sniezek & Hilary Vernon
A very delicate balance
Laurel Oldach
From the journals: JLR
Heather Masson–Forsythe

Get the latest from ASBMB Today

Enter your email address, and we’ll send you a weekly email with recent articles, interviews and more.

Latest in Science

Science highlights or most popular articles

Michel strives to be a better mentor
Award

Michel strives to be a better mentor

Dec. 1, 2021

Lea Michel has won the ASBMB Early-Career Leadership Award for her commitment to advancing the careers of women in biochemistry and molecular biology.

A new way of looking at HDL in pregnancy
Journal News

A new way of looking at HDL in pregnancy

Nov. 30, 2021

Researchers at the University of Cincinnati College of Medicine explore the compositional complexity of high-density lipoprotein in expectant mothers.

How a tiny pet store fish became the center of neuroscience research
News

How a tiny pet store fish became the center of neuroscience research

Nov. 27, 2021

The tropical zebrafish is used extensively in genetics, neuroscience and development labs worldwide.

Science is a human endeavor
Essay

Science is a human endeavor

Nov. 26, 2021

The author learned some difficult and important lessons when he decided to pursue errors in a Nobel laureate’s work.

‘Fatty retina’: A root cause of vision loss in diabetes?
Lipid News

‘Fatty retina’: A root cause of vision loss in diabetes?

Nov. 25, 2021

Abnormalities of lipid metabolism are common in diabetes, so the authors reasoned that the retina might switch its programming in response to an abundance of fuel.

From the journals: MCP
Journal News

From the journals: MCP

Nov. 24, 2021

What’s the role of CD151 in triple-negative breast cancer? How similar are nonstructural proteins between coronavirus homologs? What proteins are candidates for targeting oral cancer?