p53 Family Pathway in Cancer

Abstract

P63, P73, and P53 are members of a transcription factor family involved in cell responses to stress and differentiation. P53 is the most frequently mutated gene in human cancer (50%) and P53 activity is considered to be ubiquitously lost in cancers. P63 , P73 , and P53 genes have a dual gene structure. They encode for multiple P63, P73, or P53 proteins containing different protein domains (isoforms) owing to multiple splicing, alternative promoter, and alternative initiation of translation. In this review, we describe the different P63/P73/P53 isoforms and their roles in cancer. The interactions between P53, P63, and P73 isoforms are likely to be fundamental to our understanding in the transition between normal cell cycling and the onset of tumour formation. Our clinical data suggest that failure of appropriate expression of P53 isoforms have a role in carcinogenesis since attenuation of the WT P53 response would render the cells more susceptible to further genetic damage and therefore to neoplastic transformation and tumour progression. Tumours with abnormal P53 isoform expression would have a predicted phenotype of WT P53 by sequence but compromised P53 activity. Moreover, P53 immunostaining on tumour sections should be carefully interpreted as commonly available P53 antibodies do not detect every P53 isoform. We recommend the use of polyclonal anti‐p53CM1 antibody as it recognizes all P53 isoforms which can be localized in the nucleus and in the cytoplasm. Therefore, as P53 staining could be different from one tumour to another, we recommend the use of the secondary HRP‐conjugated anti‐rabbit IgG antibody alone as a negative control and the assessment of CM1 reactivity on positive controls. Such controls are forgotten in many immunohistochemistry studies.

Effect of Running-Induced Fatigue on Tibial Acceleration and the Role of Lower Limb Muscle Strength, Power, and Endurance

“…Session 2 included a fixed-intensity run to exhaustion at 85% of V̇O 2max . This intensity was selected so time to exhaustion could be expected between 20 and 60 min (23). All running measurements were conducted on a calibrated Woodway PPS Med motorized treadmill (Woodway, Waukesha, WI).…”