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Role of SPOP in cardiac hypertrophy and heart failure

ABSTRACT: Pressure overload-induced cardiac hypertrophy and heart failure involve profound remodeling of the myocardial proteome. To elucidate the role of the E3 adaptor protein SPOP in this process, we performed TMT-based quantitative proteomic analysis on left ventricular tissues collected four weeks after transverse aortic constriction (TAC) from Myh6-Cre control mice (n=5) and cardiac-specific SPOP knockout (cKO) mice (n=5).

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Heart, Cardiac Muscle Cell

DISEASE(S): Heart Failure

SUBMITTER: Liu jiangqi

LAB HEAD: Hao Wu

PROVIDER: PXD067120 | Pride | 2025-08-26

REPOSITORIES: Pride

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SPOP is a key trigger of pathological cardiac hypertrophy and heart failure

Project description:Cardiac hypertrophy is a pathological feature of heart failure, and dysregulation of protein turnover and autophagy has been implicated in its progression. Speckle-type POZ protein (SPOP), a substrate adaptor for the Cullin3-RING E3 ubiquitin ligase complex, plays an emerging role in protein homeostasis and transcriptional regulation. This study investigates the function of SPOP in cardiac hypertrophy and heart failure. RNA sequencing was performed to examine transcriptional changes in mouse hearts with cardiac-specific overexpression of SPOP, revealing differential expression of genes involved in autophagy, mitochondrial metabolism, and cardiac remodeling. These data provide new insights into the transcriptional landscape regulated by SPOP in the hypertrophic heart.

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Effects of SPOP on gene expression in prostate cancer

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E3 ligase substrate adaptor SPOP fine tunes the UPR of pancreatic beta cells

Project description:The Cullin 3 E3 ligase adaptor protein, SPOP, targets proteins for ubiquitination and proteasomal degradation. We previously established the β cell transcription factor (TF) and human diabetes gene PDX1 as an SPOP substrate, suggesting a functional role for SPOP in the β cell. Here, we generated a β cell specific Spop deletion mouse strain (SpopβKO) and found that Spop is necessary to prevent aberrant basal insulin secretion and for maintaining glucose- stimulated insulin secretion (GSIS) through impacts on glycolysis and glucose-stimulated calcium flux. Integration of proteomic, TF-regulatory gene network and biochemical analyses identified XBP1 as a functionally important SPOP substrate in pancreatic β cells.Further, loss of SPOP strengthened the IRE1α-XBP1 axis of unfolded protein response (UPR) signaling. ER stress promoted proteasomal degradation of SPOP, supporting a model whereby SPOP fine-tunes XBP1 activation during the UPR. These results position SPOP as a regulatorof β cell function and proper UPR activation.

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