Phosphoprotein Phosphatase 1 Complexes in Spermatogenesis

Silva, Joana Vieira; Freitas, Maria João; Fardilha, Margarida

doi:10.2174/1874467208666150126154222

Cited by 34 publications

(23 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…FASN is expressed in the mammalian liver and adipose tissue, where it regulates body fat deposition and fatty acid anabolism47. PPP1CA (phosphoprotein phosphatase 1 catalytic subunit alpha isozyme) is an isoform of PPP1C 48, which was first identified as the enzyme that converts phosphorylase A into phosphorylase B49. A number of roles have been attributed to PPP1C in the regulation of important cellular events.…”

Section: Discussionmentioning

confidence: 99%

Genome-wide detection of CNVs in Chinese indigenous sheep with different types of tails using ovine high-density 600K SNP arrays

Zhu

Fan

Yuan

et al. 2016

Sci Rep

View full text Add to dashboard Cite

Chinese indigenous sheep can be classified into three types based on tail morphology: fat-tailed, fat-rumped, and thin-tailed sheep, of which the typical breeds are large-tailed Han sheep, Altay sheep, and Tibetan sheep, respectively. To unravel the genetic mechanisms underlying the phenotypic differences among Chinese indigenous sheep with tails of three different types, we used ovine high-density 600K SNP arrays to detect genome-wide copy number variation (CNV). In large-tailed Han sheep, Altay sheep, and Tibetan sheep, 371, 301, and 66 CNV regions (CNVRs) with lengths of 71.35 Mb, 51.65 Mb, and 10.56 Mb, respectively, were identified on autosomal chromosomes. Ten CNVRs were randomly chosen for confirmation, of which eight were successfully validated. The detected CNVRs harboured 3130 genes, including genes associated with fat deposition, such as PPARA, RXRA, KLF11, ADD1, FASN, PPP1CA, PDGFA, and PEX6. Moreover, multilevel bioinformatics analyses of the detected candidate genes were significantly enriched for involvement in fat deposition, GTPase regulator, and peptide receptor activities. This is the first high-resolution sheep CNV map for Chinese indigenous sheep breeds with three types of tails. Our results provide valuable information that will support investigations of genomic structural variation underlying traits of interest in sheep.

show abstract

Section: Discussionmentioning

confidence: 99%

Genome-wide detection of CNVs in Chinese indigenous sheep with different types of tails using ovine high-density 600K SNP arrays

Zhu

Fan

Yuan

et al. 2016

Sci Rep

View full text Add to dashboard Cite

show abstract

“…2012 ) are involved in the transcription regulation of topoisomerase II, an enzyme which relaxes supercoils in DNA for transcription. As for the biomarkers in cyclophosphamide model, TSKS ( Silva et al . 2014 ) and PPP1R16B ( Boratko et al .…”

Section: Discussionmentioning

confidence: 99%

Single drug biomarker prediction for ER− breast cancer outcome from chemotherapy

Chen

Kim

Soliman

et al. 2018

Endocrine-Related Cancer

View full text Add to dashboard Cite

ER-negative breast cancer includes most aggressive subtypes of breast cancer such as triple negative (TN) breast cancer. Excluded from hormonal and targeted therapies effectively used for other subtypes of breast cancer, standard chemotherapy is one of the primary treatment options for these patients. However, as ER− patients have shown highly heterogeneous responses to different chemotherapies, it has been difficult to select most beneficial chemotherapy treatments for them. In this study, we have simultaneously developed single drug biomarker models for four standard chemotherapy agents: paclitaxel (T), 5-fluorouracil (F), doxorubicin (A) and cyclophosphamide (C) to predict responses and survival of ER− breast cancer patients treated with combination chemotherapies. We then flexibly combined these individual drug biomarkers for predicting patient outcomes of two independent cohorts of ER− breast cancer patients who were treated with different drug combinations of neoadjuvant chemotherapy. These individual and combined drug biomarker models significantly predicted chemotherapy response for 197 ER− patients in the Hatzis cohort (AUC = 0.637, P = 0.002) and 69 ER− patients in the Hess cohort (AUC = 0.635, P = 0.056). The prediction was also significant for the TN subgroup of both cohorts (AUC = 0.60, 0.72, P = 0.043, 0.009). In survival analysis, our predicted responder patients showed significantly improved survival with a >17 months longer median PFS than the predicted non-responder patients for both ER− and TN subgroups (log-rank test P-value = 0.018 and 0.044). This flexible prediction capability based on single drug biomarkers may allow us to even select new drug combinations most beneficial to individual patients with ER− breast cancer.

show abstract

“…Similar to PP1 in general, PP1γ2 activity is also regulated by its binding partners (Fardilha et al, ; Korrodi‐Gregorio et al, ; Silva, Freitas, & Fardilha, ; Vijayaraghavan et al, ). The regulators of sperm PP1γ2 identified so far are, PPP1R2 (inhibitor‐2, I2) (Vijayaraghavan et al, ; Vijayaraghavan, Mohan, Gray, Khatra, & Carr, ), PPP1R11 (inhibitor‐3, I3, tctex5) (Cheng, Pilder, Nairn, Ramdas, & Vijayaraghavan, ) and PPP1R7 (sds22) (Huang, Khatra, Bollen, Carr, & Vijayaraghavan, ; Mishra, Somanath, Huang, & Vijayaraghavan, ) which are ubiquitously expressed and evolutionarily ancient PP1 regulatory proteins (R) (Ceulemans, Stalmans, & Bollen, ).…”

Section: Introductionmentioning

confidence: 99%

“…Interestingly, the knockout of Lmtk2 (lemur tyrosine kinase 2) that is also a PP1binding partner, causes male infertility azoospermia with severe impairment of spermiogenesis beginning at the round spermatid stage similar to PP1γ knockouts (Kawa et al, 2006). Similar to PP1 in general, PP1γ2 activity is also regulated by its binding partners (Fardilha et al, 2011;Korrodi-Gregorio et al, 2014;Silva, Freitas, & Fardilha, 2014;Vijayaraghavan et al, 2007). The regulators of sperm PP1γ2 identified so far are, PPP1R2 (inhibitor-2, I2) Vijayaraghavan, Mohan, Gray, Khatra, & Carr, 2000), PPP1R11…”

mentioning

confidence: 99%

Regulators of the protein phosphatase PP1γ2, PPP1R2, PPP1R7, and PPP1R11 are involved in epididymal sperm maturation

Goswami

Korrodi‐Gregório

Sinha

et al. 2018

Journal Cellular Physiology

View full text Add to dashboard Cite

The serine/threonine protein phosphatase 1 (PP1) inhibitors PPP1R2, PPP1R7, and PPP1R11 are evolutionarily ancient and highly conserved proteins. Four PP1 isoforms, PP1α, PP1β, PP1γ1, and PP1γ2, exist; three of them except PP1γ2 are ubiquitous. The fact that PP1γ2 isoform is present only in mammalian testis and sperm led to the notion that isoform-specific regulators for PP1γ2 in sperm may be responsible for its function. In this report, we studied these inhibitors, PPP1R2, R7, and R11, to determine their spatial and temporal expression in testis and their regulatory functions in sperm. We show that, similar to PP1γ2, the three inhibitors are expressed at high levels in developing spermatogenic cells. However, the transcripts for the regulators are expressed as unique sizes in testis compared with somatic tissues. The three regulators share localization with PP1γ2 in the head and the principal piece of sperm. We show that the association of inhibitors to PP1γ2 changes during epididymal sperm maturation. In immotile caput epididymal sperm, PPP1R2 and PPP1R7 are not bound to PP1γ2, whereas in motile caudal sperm, all three inhibitors are bound as heterodimers or heterotrimers. In caudal sperm from male mice lacking sAC and glycogen synthase kinase 3, where motility and fertility are impaired, the association of PP1γ2 to the inhibitors resembles immature caput sperm. Changes in the association of the regulators with PP1γ2, due to their phosphorylation, are part of biochemical mechanisms responsible for the development of motility and fertilizing ability of sperm during their passage through the epididymis.

show abstract

Phosphoprotein Phosphatase 1 Complexes in Spermatogenesis

Cited by 34 publications

References 17 publications

Genome-wide detection of CNVs in Chinese indigenous sheep with different types of tails using ovine high-density 600K SNP arrays

Genome-wide detection of CNVs in Chinese indigenous sheep with different types of tails using ovine high-density 600K SNP arrays

Single drug biomarker prediction for ER− breast cancer outcome from chemotherapy

Regulators of the protein phosphatase PP1γ2, PPP1R2, PPP1R7, and PPP1R11 are involved in epididymal sperm maturation

Contact Info

Product

Resources

About