Activation of oncogenic signaling kinase PAK1 by ionising radiation confers an aggressive phenotype in head and neck squamous cell carcinoma.

Head and neck squamous cancers are very aggressive tumors often diagnosed in late stages with poor prognosis. HNSCCs are usually treated by a course of radiation (IR) therapy and followed by surgery. These treatment regimens fail to bring a complete response.

Mechanics of PAK1-A new molecular player in the arena of skin cancer.

Despite regular exposure of skin to solar UV-B irradiation, most individuals enjoy cancer-free existence, which is a testimony of the inherent capacity of human keratinocytes to either repair or restore cells damged by UV exposure. In this manuscript, we focus on delineating the mechanistic role of p21 activated kinase (Pak1) in UV-B provoked skin lesions. Molecular mechanistic studies revealed that Pak1 is triggered as a consequence to UV-B exposure via epidermal growth factor receptor (EGFR) and cyclobutane pyrimidine dimers (CPD) pathways, and both these membranous (EGFR) and nuclear (CPDs) events converge at Pak1 activation and contribute in a coordinated manner for yielding a complete response to UV-B via upregulating Ataxia-Telangiectasia and Rad3 related (ATR).

KIBRA attains oncogenic activity by repressing RASSF1A.

Background: KIBRA-initially identified as a neuronal associated protein is now shown to be functionally associated with other tissue types as well. KIBRA interacts with dyenin light chain 1 and this interaction is essential for oestrogen receptor transactivation in breast cancer cells. KIBRA as a substrate of Cdk1, Aurora kinase and ERK plays an important role in regulating cell cycle, cell proliferation and migration.

Molecular Mechanism of Regulation of MTA1 Expression by Granulocyte Colony-stimulating Factor.

Parkinson disease (PD) is a neurodegenerative disorder with loss of dopaminergic neurons of the brain, which results in insufficient synthesis and action of dopamine. Metastasis-associated protein 1 (MTA1) is an upstream modulator of tyrosine hydroxylase (TH), the rate-limiting enzyme in dopamine synthesis, and hence MTA1 plays a significant role in PD pathogenesis. To impart functional and clinical significance to MTA1, we analyzed MTA1 and TH levels in the substantia nigra region of a large cohort of human brain tissue samples by Western blotting, quantitative PCR, and immunohistochemistry.

Phosphorylation-Dependent Regulation of the DNA Damage Response of Adaptor Protein KIBRA in Cancer Cells.

Multifunctional adaptor proteins encompassing various protein-protein interaction domains play a central role in the DNA damage response pathway. In this report, we show that KIBRA is a physiologically interacting reversible substrate of ataxia telangiectasia mutated (ATM) kinase. We identified the site of phosphorylation in KIBRA as threonine 1006, which is embedded within the serine/threonine (S/T) Q consensus motif, by site-directed mutagenesis, and we further confirmed the same with a phospho-(S/T) Q motif-specific antibody.