PCTAIRE1 promotes mitotic progression and resistance against antimitotic and apoptotic signals

Gillani, Syed Qaaifah; Reshi, Irfana; Nabi, Nusrat; Nisa, Misbah Un; Sarwar, Zarka; Bhat, Sameer Ahmed; Roberts, Thomas M.; Higgins, Jonathan M.G.; Andrabi, Shaida

doi:10.1242/jcs.258831

Cited by 4 publications

(4 citation statements)

References 41 publications

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“…The LKB1‐AMP kinase axis negatively regulates this pathway through the phosphorylation and activation of TSC1/2 complex (Inoki et al 2003). In addition, we have also found out that AKT1 and LKB1 regulate protein levels of some proteins (e.g DBC1/CCAR2 and PCTAIRE1/CDK16) in contrasting ways (Gillani et al 2022; Sarwar et al 2022). We therefore tested the effect of LKB1 on lipin‐1 protein levels.…”

Section: Resultsmentioning

confidence: 98%

Lipin-1 stability and its adipogenesis functions are regulated in contrasting ways by AKT1 and LKB1

Nisa

Gillani

Nabi

et al. 2022

J. Cell Commun. Signal.

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Lipin‐1 is a protein that plays a critical role in many cellular functions. At molecular level, it acts as a phosphatidic acid phosphohydrolase and a transcriptional coactivator. The functions of lipin‐1 are largely dependent upon its subcellular localization, post‐translational modifications like phosphorylation and acetylation, and also on its interaction with other proteins such as 14‐3‐3. However, the kinases and phosphatases that are responsible for these post translational modifications are not entirely known. Using bioinformatics and other biochemical approaches, we demonstrate lipin‐1 as a novel target for AKT1 and LKB1. While AKT1 stabilizes lipin‐1, LKB1 causes its degradation. Interestingly, our findings further show that lipin‐1 enhances AKT1 activity as can be seen by increased phosphorylation of the substrates of AKT1. Taken together, our results suggest that lipin‐1 plays an important role in the regulation of PI3K‐AKT‐mTOR pathway, which is dysregulated in majority of cancers. Therefore, understating the role of lipin‐1 may provide new and important insights into the regulation and functions of the PI3K‐mTOR pathway, which is one of the major targets for anti‐cancer drug development strategies.

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Section: Resultsmentioning

confidence: 98%

Lipin-1 stability and its adipogenesis functions are regulated in contrasting ways by AKT1 and LKB1

Nisa

Gillani

Nabi

et al. 2022

J. Cell Commun. Signal.

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“…In addition to their role in the cell cycle, Cdks coordinate with stemness 48 , cell polarity 49,50 , and cell fate specification/determination [51][52][53][54] . Cdk16 (also known as PCTAIRE-1) was previously reported to participate in secretory cargo transport 55 , autophagy 28 , spermatogenesis 28,56 , and tumor proliferation 57 . In this work, we uncovered a new role for Cdk16 and Cdk2 in modulating Hwa/β-catenin signaling.…”

Section: Discussionmentioning

confidence: 99%

A phosphorylation switch of Huluwa receptor for embryonic axis induction

Chen,

Li,

Yan

et al. 2024

Preprint

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Embryonic axis formation is essential for patterning and morphogenesis in vertebrates and is tightly regulated by the dorsal organizer. Previously, we demonstrated that maternally derived Huluwa (Hwa) acts as a dorsal determinant, dictating axis formation by activating β-catenin signaling in zebrafish and Xenopus. However, the mechanism of activation and fine regulation of the Hwa receptor remain unclear. In a systematic mutation screen, a mutation at the 168th serine (Ser168) in the PPNSP motif of Hwa dramatically abolished its axis-inducing activity. Mechanistically, mutating the Ser168 residue reduced its binding affinity to Tankyrase 1/2 and the degradation of the Axin protein, weakening β-catenin signaling activation. Furthermore, the Ser168 site was confirmed to be phosphorylated via LC-MS/MS and immunoblotting with a phosphorylation-specific antibody. Additionally, several kinases, including Cdk16, Cdk2, and GSK3β, were found to enhance Ser168 phosphorylation in vitro and in vivo, enhancing Hwa's activity in β-catenin signaling and axis induction. Meanwhile, the use of dominant-negative Cdk16 and pHwa (Ser168) antibodies reduced Hwa's function. In summary, Ser168 acts as a phosphorylation switch in Hwa/β-catenin signaling for embryonic axis induction, involving multiple kinases to ensure developmental robustness.

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“…Cyclin Y, p35 Promotes cell proliferation (Gillani et al, 2022;Yanagi et al, 2014) Deactivates p27 and p53 tumor suppressors (J. Xie et al, 2018;Yanagi et al, 2014) Involved in terminal differentiation in spermatogenesis (Mikolcevic, Rainer, & Geley, 2012;Mikolcevic, Sigl, et al, 2012) Implicated in neural outgrowth (Graeser et al, 2002;Mokalled et al, 2010) Functions in vesicular trafficking (Y.…”

Section: Cdk16mentioning

confidence: 99%

“…Xie et al, 2018;Yanagi et al, 2014) Involved in terminal differentiation in spermatogenesis (Mikolcevic, Rainer, & Geley, 2012;Mikolcevic, Sigl, et al, 2012) Implicated in neural outgrowth (Graeser et al, 2002;Mokalled et al, 2010) Functions in vesicular trafficking (Y. Liu et al, 2006;Ou et al, 2010;Palmer et al, 2005;Shehata et al, 2019) Implicated in brain development (Cole, 2009;Fu et al, 2011;Le Bouffant et al, 2000;Mokalled et al, 2010;Shehata et al, 2015Shehata et al, , 2019 Suppresses apoptosis (Gillani et al, 2022;Yanagi & Matsuzawa, 2015) Implicated in glucose homeostasis (X. Y. Chen et al, 2012;Tang et al, 2006) Promotes myogenesis (Shimizu et al, 2014)…”

Section: Cdk16mentioning

confidence: 99%

Cyclin‐dependent kinases: Masters of the eukaryotic universe

Pluta,

Studniarek,

Murphy

et al. 2023

WIREs RNA

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A family of structurally related cyclin‐dependent protein kinases (CDKs) drives many aspects of eukaryotic cell function. Much of the literature in this area has considered individual members of this family to act primarily either as regulators of the cell cycle, the context in which CDKs were first discovered, or as regulators of transcription. Until recently, CDK7 was the only clear example of a CDK that functions in both processes. However, new data points to several “cell‐cycle” CDKs having important roles in transcription and some “transcriptional” CDKs having cell cycle‐related targets. For example, novel functions in transcription have been demonstrated for the archetypal cell cycle regulator CDK1. The increasing evidence of the overlap between these two CDK types suggests that they might play a critical role in coordinating the two processes. Here we review the canonical functions of cell‐cycle and transcriptional CDKs, and provide an update on how these kinases collaborate to perform important cellular functions. We also provide a brief overview of how dysregulation of CDKs contributes to carcinogenesis, and possible treatment avenues.This article is categorized under: RNA Interactions with Proteins and Other Molecules > RNA‐Protein Complexes RNA Processing > 3′ End Processing RNA Processing > Splicing Regulation/Alternative Splicing

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PCTAIRE1 promotes mitotic progression and resistance against antimitotic and apoptotic signals

Cited by 4 publications

References 41 publications

Lipin-1 stability and its adipogenesis functions are regulated in contrasting ways by AKT1 and LKB1

Lipin-1 stability and its adipogenesis functions are regulated in contrasting ways by AKT1 and LKB1

A phosphorylation switch of Huluwa receptor for embryonic axis induction

Cyclin‐dependent kinases: Masters of the eukaryotic universe

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